Category Archives: Stem Cell Medicine

BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership – Diagnostic and Interventional Cardiology

March 15, 2024 BioCardia, Inc., a biotechnology company focused on advancing late-stage cell therapy interventions for cardiovascular disorders, andStemCardia, Inc., a biotechnology company focused on cell and gene therapy to re-muscularize the failing heart, today announced a long-term partnership to advance StemCardias investigational pluripotent stem cell product candidate for the treatment of heart failure.

Under the partnership, BioCardia is the exclusive biotherapeutic delivery partner for StemCardias cell therapy candidate through studies expected to result in FDA approval of an investigational new drug application (IND) and the anticipated Phase I/II clinical development to follow.

BioCardia has established safe and minimally invasive delivery of cellular medicines directly into the heart, said Chuck Murry, MD, PhD, StemCardias Founder and CEO. Having worked with BioCardia to successfully deliver our bona fide cardiac muscle cells in large animal models of heart failure, we are excited for this partnership to accelerate clinical development and broaden future commercial access to an off-the-shelf heart regeneration treatment.

StemCardias team encompasses recognized leaders in the field of cardiac regenerative medicine who are pursuing an elegant strategy to repair the failing heart. We look forward to supporting their efforts with our experienced team and proven, proprietary Helix biotherapeutic delivery system, said BioCardia CEO Peter Altman, PhD. This partnership is expected to enhance future treatment options for millions of people suffering from heart failure, offset the costs of biotherapeutic delivery development for our own programs, and provide our investors with meaningful revenue sharing should our efforts together contribute to StemCardias successful therapeutic development.

For more information:www.biocardia.com

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BioCardia and StemCardia Announce Biotherapeutic Delivery Partnership - Diagnostic and Interventional Cardiology

Striving to Support Gender Equality in Health Care – City of Hope

Nadia Carlesso, M.D., Ph.D.

As a member of the newest class of 24 women selected nationwide to participate in the Carol Emmott Fellowship, Nadia Carlesso, M.D., Ph.D., wants to take this unique and competitive opportunity to move the needle in advancing diversity, equity and inclusion (DEI) on both sides of the research bench.

The Carol Emmott Foundation is a national nonprofit organization that is dedicated to achieving fully inclusive gender equality in health care leadership and governance. The fellowship includes a 14-month experience in which fellows can receive mentorship for their personal projects that support gender equity in health care.

Based on the Duarte, California, campus, Carlesso joined City of Hope in 2016. She is currently professor and chair of the Department of Stem Cell Biology and Regenerative Medicine.

As a scientist in the stem cell field and as chair of the Department of Stem Cell Biology and Regenerative Medicine, I feel the responsibility and commitment to contribute, in the measure I can, to decreasing health disparities in the areas of innovative cell and gene therapies, Carlesso said.

Carlesso said health disparities exist in some part due to the prohibitive costs associated with getting treatment and participating in clinical trials.

We are living in exciting times in terms of the progress and availability of cell and gene therapies potentially curative therapies, she said. But these products have a high cost that can unfortunately widen the care gap. Access to innovative therapies is expensive for many complex reasons. As a community, scientists, technologists and health care professionals must come together to be part of the solution.

There's no easy answer, and not a problem that will be resolved tomorrow, but the conversation has started within scientific circles, and Carlesso wants to further that dialogue and parlay it into actions that can truly make progress.

One step in the right direction is to increase diversity within the scientific community in all aspects, in the name of advancing clinical knowledge.

City of Hope is a diverse and inclusive organization, and I would like to leverage that commitment, Carlesso said. The Emmott Fellowship has given me the opportunity to focus more intently on growing the diversity within our scientific environment.

Innovative biomedical research flourishes when people with different perspectives, experience and skills are empowered to explore new ideas and to work collaboratively and inclusively, she continued. Recruiting, training, retaining and nurturing a workforce representing all dimensions of diversity is critical for the development and implementation of leading-edge therapies that can reach underserved populations. These communities have not had their voices heard: Targeting these communities to be active participants of this specialized workforce and future leaders in this sector is key to decrease barriers to health equity.

Another key step toward this goal is to increase awareness among these communities that their voices are important.

There is not sufficient knowledge out there that they are needed, Carlesso explained. There are cultural biases that have to be overcome. If patients can see themselves in our medical and scientific staff, they will feel more represented and more comfortable that their best interests are at heart.

As an Emmott Fellow, Carlesso said she has identified three areas that she wishes to address in her research project.

The first part is for me to get the numbers, to look at the current diversity within our clinical trials, within our GMP teams, clinical trial coordinators, research nurses, clinicians and basic scientists, she said. At any given time, we have more than 30 investigational new drug applications and 300 clinical trials going on. I want to take advantage of this ideal setting and generate a complete database of the progress weve made, the challenges we still face, and where the bottlenecks are that are compromising diversity and inclusion at all levels.

Establishing a discourse, conversations among peers, is essential to stimulate a reaction toward diversity in research that will benefit all of us, Carlesso said.

A cohesive stem cell research community is critical not only to generate discoveries but also to bring awareness in health disparities and generate synergistic efforts to tackle this problem, she said.

Carlesso maintained that we can empower patients by empowering a diverse workforce, and one way we can do that is to recruit individuals from diverse backgrounds into careers in science, technology, engineering and math (STEM).

A powerful way to give a voice to underserved communities and people of underrepresented backgrounds, and to mitigate health disparities, is to train a workforce that represents them, she said. If underserved families start to have kids going to high school and college doing internships in science and contemplating a carrier in nursing, biomanufacturing, research, then they will have more information, more access and will be less afraid to ask and to pursue more advanced therapeutic solutions or participate to clinical trials.

City of Hope is committed to training the next generation of leaders in stem cells, gene therapy and regenerative medicine, and in fostering an inclusive and safe environment that embraces diversity. Our laboratories host interns every year from the California Institute for Regenerative Medicine bridge program, for example, and we recruit from all communities for our Eugene and Ruth Roberts Summer Student Academy. We also partner with California State Universities in our area and local high schools near the Duarte campus to grow the interest in STEM careers.

As an organization, we need to know that our research has great potential and is helping to close the care gap between socially economically disadvantaged groups and others, Carlesso said. Knowing where we are now is important, so we can define where we are going and how we are going to get there.

I am very excited and thankful to have been chosen for the Emmott Fellowship and the opportunities it represents, she said. I am thrilled and look forward to what I can learn, accomplish and change for the better in my work.

Learn more about the Carol Emmott Fellowship, Carlesso and other members of the Class of 2024, here.

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Striving to Support Gender Equality in Health Care - City of Hope

Transitioning from traditional surgical methods to the innovative use of stem cells – pharmaphorum

Patient lives are being transformed by a transitioning from traditional surgical methods to the innovative use of stem cells.

In todays podcast, host Nicole Raleigh welcomes Dr Jeffrey Gross, founder of ReCELLebrate, neurological surgeon, and expert in the field of regenerative medicine, to discuss this development. Their conversation delves into the recent appetite for the use of stem cells for longevity and explores the health span notion that is being ever more frequently spoken of.

But, essentially, regenerative medicine deals with the functional restoration of specific tissue and/or organ of patients, patients who might be suffering from severe injuries or chronic disease conditions, and who are in a state where the bodys own regenerative responses do not suffice and that is where stem cells, endorsed with indefinite cell division potential and the ability to transdifferentiate into other types of cells, are emerging as a frontline regenerative medicine source.

Yet, when it come to health and vitality, and to epigenetics and prolonged health, scepticism remains and Dr Gross attempts to demystify the landscape for listeners on that, too, including especially the most regenerative source of stem cells: the placenta.

You can listen to episode 121a of thepharmaphorum podcastin the player below, download the episode to your computer, or find it - and subscribe to the rest of the series - iniTunes,Spotify,acast,Stitcher,andPodbean.

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Transitioning from traditional surgical methods to the innovative use of stem cells - pharmaphorum

Pelage Pharmaceuticals Announces $16.75M Series A Financing led by GV to Revolutionize Regenerative Medicine … – BioSpace

LOS ANGELES , Feb. 27, 2024 /PRNewswire/ -- Pelage Pharmaceuticals, a clinical-stage regenerative medicine company pioneering a new generation of treatments for hair loss, announced today that the company has closed a $16.75 million Series A financing led by GV with participation from Main Street Advisors, Visionary Ventures and YK BioVentures, to advance a first-in-class treatment for androgenetic alopecia or pattern baldness, and other types of alopecia including chemotherapy-induced hair loss.

"Our scientific co-founders have uncovered a unique biological mechanism with the potential to reactivate hair growth in people with alopecia," said Daniel Gil, Ph.D., Chief Executive Officer, Pelage Pharmaceuticals. "We are pleased to announce that we have completed a first-in-human Phase 1 clinical trial that demonstrated seven days of topical dosing with PP405 was safe and well-tolerated, and showed statistically significant activation of hair follicle stem cells. With the support of GV, Main Street Advisors and other top-tier investors, we expect to advance our lead program to a Phase 2a clinical trial in the second half of this year."

The Phase 1 trial evaluating PP405, a novel topical agent designed to treat androgenetic alopecia and other forms of hair loss, showed 0.05% PP405 topical treatment for seven days is safe and tolerable with no adverse events, and provided confirmation of a daily dosing regimen. Importantly, the study demonstrated biological activity, proof of mechanism of action seen in preclinical studies, and showed treatment with PP405 stimulated statistically significant activation of a critical hair follicle stem cell activation marker. Translational data will be presented at the American Academy of Dermatology meeting in March.

Androgenetic alopecia, also known as pattern balding, is the most common form of alopecia and accounts for more than 90% of all hair loss, impacting both men and women. Additionally, PP405 may also have applications for other types of hair loss such as telogen effluvium (stress-induced hair loss) and chemotherapy-induced hair loss.

"What we've observed is that in people who experience hair loss, the actual hair follicle stem cells are still present but have reverted to a dormant state. We have uncovered a small molecule able to stimulate cellular metabolism to re-awaken hair follicle stem cells and spur new hair growth," said William Lowry, Ph.D., scientific co-founder, Pelage Pharmaceuticals. The discovery was made by Drs. Lowry, Heather Christofk and Michael Jung, of the University of California, Los Angeles. PP405 is designed to inhibit the mitochondrial pyruvate carrier (MPC) to specifically reactivate the dormant hair follicle stem cells.

"Hair loss is an incredibly common health problem with few effective solutions," said Cathy Friedman, Executive Venture Partner, GV and Board Director, Pelage Pharmaceuticals. "GV is excited by the incredible science behind the Pelage technology. Pelage is pioneering an innovative approach with the potential to disrupt the treatment landscape, moving beyond agents that merely slow the progression of hair loss to a treatment solution that actually helps to regrow hair."

Along with the financing and Phase 1 topline data, Pelage has announced the appointment of Qing Yu Christina Weng, M.D., as the company's Chief Medical Officer (CMO). Dr. Weng is a physician-scientist, Harvard-trained board-certified dermatologist at Massachusetts General Hospital, and faculty at Harvard Medical School. In addition to her clinical expertise, Dr. Weng brings a background in corporate startup strategy and business development. At Pelage, Dr. Weng's experience will inform the company's development of PP405 as it advances to Phase 2 studies.

"The current therapeutic landscape is dominated by reformulations of existing products. Pelage is built on rigorous science and offers the opportunity to target the follicle stem cells directly," said Dr. Weng. "I am thrilled to work with the Pelage team to advance this discovery in pursuit of a novel non-invasive solution for all people who experience hair loss."

About Pelage Pharmaceuticals

Pelage Pharmaceuticals is a clinical-stage regenerative medicine company developing novel treatments for hair loss including androgenetic alopecia and chemotherapy-induced-alopecia. With a focus on molecular and stem cell biology, Pelage is advancing a new class of treatments designed to reactivate dormant hair follicle stem cells and restore the body's ability to naturally grow hair. Its lead program, PP405, is currently in clinical trials. Through its rigorous scientific foundation, topical formulation, and novel mechanism of action, Pelage is pioneering first-in-class hair growth solutions for people of all hair types experiencing hair loss.

About PP405

PP405 is a novel, non-invasive, topical small molecule designed to reactivate dormant hair follicle stem cells and restart hair growth. Through a regenerative medicine approach, the treatment focuses on addressing the metabolic processes that regulate the activation and inactivation phases of hair follicle stem cells. Early results from a Phase 1 trial show that PP405 was well-tolerated and demonstrated statistically significant activation of hair follicle stem cells. In 2018, Pelage Pharmaceuticals licensed the intellectual property to PP405 and related topical small molecules from the UCLA Technology Development Group.

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Pelage Pharmaceuticals Announces $16.75M Series A Financing led by GV to Revolutionize Regenerative Medicine ... - BioSpace

Summer research program open to students interested in stem cell and regenerative medicine research – The Daily | Case Western Reserve University

The ENGAGE summer research training program supports undergraduate, masters and medical students interested in stem cell and regenerative medicine research. Students are provided opportunities for scientific growth by working with our renowned scientific investigators.

The National Center for Regenerative Medicine funds these student research training projects. Each award provides $4,000 as a trainee summer stipend. An additional $500 is given to the hosting laboratory for research materials and supplies. The funded project is expected to last eight weeks.

Learn more about the ENGAGE summer program and find out how to apply. The deadline to apply is March 27 at 11:59 p.m.

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Summer research program open to students interested in stem cell and regenerative medicine research - The Daily | Case Western Reserve University

UC Irvine advances stem cell research with $4 million CIRM grant for shared resources lab – UCI News

Irvine, Calif., Feb. 26, 2024 The University of California, Irvine has received a five-year, $4 million grant from the California Institute for Regenerative Medicine to establish a shared resources lab in the Sue & Bill Gross Stem Cell Research Center. The facility will offer essential technologies and training for the development of novel in vitro stem cell-based modeling that will serve researchers across the campus and the state.

Stem cells possess the potential to transform into particular cell types, offering promising avenues for rejuvenating and restoring tissues harmed by injury or affected by disease, said principal investigator Craig Walsh, UCI professor of molecular biology and biochemistry. Utilizing stem cell modeling facilitates the development of new treatments and drug screening platforms and also provides deeper understanding of both discovery and translational research processes.

The grant will expand the UCI stem cell centers current lab capabilities, including the addition of new and upgraded equipment, instrumentation and components, and establish new services and user training in four key areas: foundational technologies, bioengineering and organoids, gene editing, and high-dimensional spatial analysis. Training is essential to characterize stem cell models, develop novel regenerative medicine therapeutics, and ensure that theres a workforce capable of implementing new strategies.

Our state-of-the-art facility and cutting-edge training opportunities demonstrate our commitment to advancing stem cell research and discovery, as well as to education and skill enhancement, said Aileen Anderson, Ph.D., director of the UCI stem cell center and professor of physical medicine & rehabilitation at the UCI School of Medicine.

The impact of the labs initiatives will foster collaborations with academic and industrial partners throughout California and leverage existing training programs such as CIRM Bridges to accelerate innovation. This effort underscores the scientific communitys drive to transform the landscape of regenerative medicine.

The Sue & Bill Gross Stem Cell Research Centers shared resources lab will contribute to the broader CIRM mission to develop a stem cell-based modeling ecosystem throughout California, supporting the basic and translational research necessary to advance scientific discoveries and the development of new therapeutic solutions for unmet medical needs, ranging from neurological diseases to cancer.

About UCIs Brilliant Future campaign:Publicly launched on Oct. 4, 2019, the Brilliant Future campaign aims to raise awareness and support for UCI. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UCI seeks to reach new heights of excellence instudent success, health and wellness, research and more. The School of Biological Sciences plays a vital role in the success of the campaign. Learn more by visitinghttps://brilliantfuture.uci.edu/school-of-biological-sciences.

About the University of California, Irvine:Founded in 1965, UCI is a member of the prestigious Association of American Universities and is ranked among the nations top 10 public universities byU.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide.For more on UCI, visitwww.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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UC Irvine advances stem cell research with $4 million CIRM grant for shared resources lab - UCI News

Top Stem Cell Clinics in the World: Pioneering Future Medicine – Corporate Wellness Magazine

The realm of regenerative medicine, particularly stem cell therapy, has witnessed exponential growth over the past few decades. Stem cells offer the remarkable potential to repair, regenerate, and rejuvenate tissues and organs, presenting new horizons in treating various diseases and injuries. This article delves into the pioneering world of stem cell clinics, showcasing institutions leading the charge in harnessing the transformative power of stem cell therapies. These clinics are not just medical facilities; they are the epicenters of innovation and research that are reshaping the future of medicine.

Stem cell clinics across the globe are pushing the boundaries of medical science. They specialize in harvesting, manipulating, and deploying stem cells to treat a myriad of conditions, from chronic diseases to orthopedic injuries and beyond. These institutions are characterized by their state-of-the-art facilities, interdisciplinary teams of experts, and a commitment to research and development.

The top stem cell clinics are renowned for their pioneering work in developing and applying cutting-edge treatments. They utilize a variety of stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells, each serving different therapeutic purposes. Treatments range from repairing damaged cartilage in joints, treating autoimmune diseases, to pioneering efforts in neurodegenerative diseases like Parkinsons and Alzheimers.

Research is a cornerstone of these leading clinics. They are often affiliated with academic institutions and participate in global research initiatives, contributing to the growing body of scientific literature on stem cell therapies. These clinics are at the forefront of translating laboratory discoveries into clinical applications, ensuring that treatments are both safe and effective.

The global nature of top stem cell clinics reflects the universal demand for advanced medical treatments. Many of these clinics have become hubs for medical tourism, attracting patients worldwide seeking access to the latest in regenerative medicine. This international aspect underscores the importance of regulatory standards and ethical considerations in stem cell therapy, areas in which these clinics lead by example.

Adhering to stringent ethical and regulatory standards is paramount. The best stem cell clinics operate with transparency, obtaining proper consents, and following rigorous protocols to ensure patient safety and treatment efficacy. They navigate the complex landscape of stem cell research and therapy with integrity, contributing to the field's ethical advancement.

What sets these clinics apart is their holistic, patient-centric approach. Understanding that each patient's needs and conditions are unique, they offer personalized treatment plans. This bespoke approach ensures that patients receive the most appropriate stem cell therapy, maximizing the potential for successful outcomes.

As the field of regenerative medicine continues to evolve, so too will the role of stem cell clinics. With ongoing research and technological advancements, the potential applications of stem cell therapy will expand, offering hope for incurable and untreatable conditions. These clinics are not just treating patients; they are shaping the future of healthcare.

In conclusion, The top stem cell clinics in the world are more than medical facilities; they are beacons of hope for patients and catalysts for change in the medical community. Their pioneering work in regenerative medicine exemplifies the power of stem cell therapy to transform lives. As they continue to innovate and lead, the promise of future medicine becomes increasingly tangible, marking a new era in healthcare where regeneration and healing are at the forefront.

Given his unparalleled expertise and success in treating elite athletes and high-profile individuals, we highly recommend Dr. Chad Prodromos for anyone seeking top-tier stem cell treatment. His work at the Prodromos Stem Cell Institute is at the forefront of regenerative medicine, offering innovative solutions for a range of conditions. To explore how Dr. Prodromos can assist in your health journey, consider reaching out through his clinic's website for more detailed information and to schedule a consultation. visit Prodromos Stem Cell Institute.

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Top Stem Cell Clinics in the World: Pioneering Future Medicine - Corporate Wellness Magazine

The Promise and Reality of Stem Cell Therapy: What You Need to Know – Corporate Wellness Magazine

In the rapidly evolving world of medicine, stem cell therapy emerges as a beacon of hope for individuals suffering from a range of chronic diseases, injuries, and conditions previously thought untreatable through conventional methods. As the medical community continues to unlock the potential of stem cells, patients and healthcare professionals alike are keenly interested in understanding the promises and realities of this innovative treatment option. This article delves into the intricacies of stem cell therapy, offering a comprehensive overview of what patients need to know.

Stem cell therapy, a cornerstone of regenerative medicine, utilizes stem cells to repair or replace damaged cells, tissues, or organs. This approach has the potential to treat a variety of conditions, including but not limited to, degenerative diseases, spinal cord injuries, and heart disease. The promise of stem cell therapy lies in its ability to promote healing and regenerate damaged tissues, offering hope for long-term recovery and a significant improvement in quality of life.

Stem cells can be classified into two main categories: autologous and allogeneic. Autologous stem cells are derived from the patient's own body, minimizing the risk of immune rejection. Allogeneic stem cells, on the other hand, are sourced from a donor. Each type has its applications and considerations, including ethical concerns, availability, and potential for immune response.

The allure of stem cell therapy lies in its versatility and the potential for groundbreaking treatment outcomes. It offers prospects for regenerating damaged heart tissue, treating neurodegenerative diseases like Parkinson's and Alzheimer's, and repairing bones and cartilage in conditions such as osteoarthritis. Moreover, ongoing research continues to explore its efficacy in treating autoimmune diseases, diabetes, and other chronic conditions.

While the potential of stem cell therapy is vast, it's essential for patients and healthcare providers to navigate its realities with a clear understanding. The field is still in its experimental stages for many applications, meaning that treatments may not always lead to successful outcomes. There are also risks associated with stem cell therapy, including infection, immune rejection, and the possibility of the cells differentiating into unintended tissue types.

The ethical and legal landscape surrounding stem cell therapy is complex, involving debates over the use of embryonic stem cells, consent, and the potential for misuse. Legislation varies by country, impacting the availability and regulatory oversight of stem cell treatments. Patients considering treatment abroad should be well-informed about the legal and ethical frameworks governing stem cell therapy in their chosen destination.

As stem cell therapy becomes more sought-after, medical tourism plays a significant role in connecting patients with treatment options worldwide. It's crucial for those considering treatment abroad to conduct thorough research, ensuring the chosen facility adheres to international standards, employs qualified professionals, and operates with transparency regarding treatment outcomes and potential risks.

For patients exploring stem cell therapy, setting realistic expectations is paramount. Success rates can vary widely depending on the condition being treated, the type of stem cells used, and the patient's overall health. It's important to engage in detailed discussions with healthcare providers to understand the potential benefits and limitations of the treatment.

In conclusion, Stem cell therapy represents a frontier in modern medicine, offering promising solutions for conditions once deemed incurable. However, it's accompanied by a spectrum of ethical, legal, and practical considerations that patients must navigate. By staying informed and consulting with medical professionals, individuals can make educated decisions about pursuing stem cell therapy, fully aware of its promises and realities. As the field continues to evolve, the hope is that advancements in research and regulatory frameworks will further unlock the potential of stem cells, making safe and effective treatments more accessible to those in need.

Given his unparalleled expertise and success in treating elite athletes and high-profile individuals, we highly recommend Dr. Chad Prodromos for anyone seeking top-tier stem cell treatment. His work at the Prodromos Stem Cell Institute is at the forefront of regenerative medicine, offering innovative solutions for a range of conditions. To explore how Dr. Prodromos can assist in your health journey, consider reaching out through his clinic's website for more detailed information and to schedule a consultation. visit Prodromos Stem Cell Institute.

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The Promise and Reality of Stem Cell Therapy: What You Need to Know - Corporate Wellness Magazine

Innovative therapy targets and destroys leukemia stem cells – News-Medical.Net

Findings

Scientists at City of Hope, one of the largest cancer research and treatment organizations in the United States, have devised an innovative approach to target and destroy hard-to-kill leukemia stem cells. The journal Blood published the preclinical findings today.

By overcoming challenges, such as drug resistance and treatment relapse common to patients with acute myeloid leukemia (AML), the therapy method could provide a less toxic and more effective approach for older and sicker patients who don't quality for stem cell transplants -; currently the only cure for AML available.

Type II interferon (IFNy), a substance produced by immune cells, disrupts the leukemia stem cells' ability to divide and spread cancer. However, IFNy also stimulates CD38, a protein that suppresses the immune cells' ability to mount a response against infection.

To overcome this challenge, the researchers designed a T cell engager antibody called CD38-BIONIC that creates a bridge between the T cells and the leukemia stem cells expressing CD38, enabling the immune system to kill off the cancer cells. Equally important, the approach did not damage healthy early blood stem cells or immune cells in human tissue or AML mouse models.

When leukemia invades the bone marrow, it produces abnormal early blood cells called blasts that are CD38-positive. These divide rapidly and are easy to target. In contrast, the leukemia stem cells that form cancer stubbornly resist treatment and are CD38-negative.

"CD38 has successfully been exploited as a therapeutic target in multiple myeloma and other forms of leukemia," said Flavia Pichiorri, Ph.D., M.S., who co-led the study with fellow investigators John Williams, Ph.D., and Guido Marcucci, M.D. -; all professors at City of Hope. "Because AML stem cells are mainly CD38-negative, however, scientists have not prioritized CD38 as a therapeutic target for relapsed acute myeloid leukemia."

In the current study, CD38-BIONIC binds to the CD38-positive blasts. This triggers the T cells to release IFNy, which converts the immature leukemia stem cells from CD38-negative to CD38-positive. In one stroke, the engineered antibody unmasks all the leukemia cells, exposing them to treatment.

We believe that the compact format of BIONIC leads to an efficient immune system connection point with the CD38-positive blast, which drives IFNy production. The leukemia stem cells react to the IFNy, painting themselves with CD38, which in turn allows them to be targeted by the CD38-CD3 BIONIC."

John Williams, Ph.D., Professor,City of Hope

Marcucci added, "This novel mechanism and the targeting by City of Hope's homegrown approach will allow us to eliminate otherwise dormantleukemia stem cells. Our hope and goal is that eradication of leukemia stem cells will decrease and even eliminate the risk of disease relapse in patients with AML, but much more research needs to be done to translate our preclinical research into human treatment."

Despite recent Food and Drug Administration-approved therapies, only 30% of adult patients with AML survive five years past diagnosis. More than half of patients relapse after treatment, and treatment resistance remains a major challenge. Patients often must remain hospitalized because their blood and immune systems are compromised by the cancer and its therapies.

While stem cell transplants from a bone marrow donor can prolong life, many older patients do not qualify due to their compromised health or the inability to find a matched donor. The majority of patients with AML urgently need less toxic and more effective treatments.

The research was partly supported by grants from the National Institutes of Health (R01-CA238429, R50-CA252135, P30CA033572), National Cancer Institute,Nason-Hollingsworth Project for Multiple Myeloma project and City of Hope's Integrated Drug Development Venture program.

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Innovative therapy targets and destroys leukemia stem cells - News-Medical.Net

Study reveals distinct molecular features of proximal and distal colon cancers – News-Medical.Net

The colon is often thought of as one organ, but the right and left parts of the colon have different molecular features in cancers. New research in mice from investigators at theJohns Hopkins Kimmel Cancer Centerdemonstrates that these regions also have distinct transcriptional programs, or cellular processes, that regulate the development of normal and cancerous cells.

The transcription factor CDX2 -; which plays an important role in the development and function of the digestive system -; is a key mediator of these differences in proximal (right) colon stem cells, according to the research, which waspublished online Feb. 15inNature Communications. CDX2 has distinct roles in regulating stem cell differentiation in the proximal and distal (left) colon regions, the study finds. This distinction in stem cell regulation could help explain various features of colon cancers housed in these two areas of the colon.

In cancers, the proximal and distal regions of the colon have a tendency to house different gene mutations, explains senior study authorHariharan Easwaran, Ph.D., an associate professor of oncology at theJohns Hopkins University School of Medicine. For example, mutations in the BRAF gene contribute to cancers mainly in the proximal region, while mutations in the KRAS gene more commonly contribute to cancers in the distal colon and rectal regions. There also are a lot of epigenetic differences -; modifications to DNA that regulate whether genes are turned on or off -; between the two regions. The BRAF-driven proximal colon cancers are associated with a very high frequency of DNA methylation, a chemical modification of DNA, in gene regulatory elements such as the CpG islands.

BRAF mutations are associated with a poor prognosis in colon cancers. However, drugs that target mutations in BRAF haven't performed as well in colon cancers compared to other types of cancer such as melanoma, Easwaran says. "Dissecting this biology is important to understanding the basis for key differences in the molecular genetics and clinical features of these cancers, and in general for understanding why cancers arising within highly similar tissues in the colon may exhibit distinct features," he says.During the study, investigators derived proximal and distal colon organoids from 2-month-old mice, and introduced the BRAF cancer-causing gene. Organoids are lab-grown clusters of cells that resemble specific organs, such as the colon, and can grow indefinitely. They mimic the stem cell and differentiation patterns of the original tissue source, in this case, colon. The investigators identified small differences in gene expression in the proximal and distal colon-derived organoids. However, loss of CDX2 produced distinct differences in regulation of genes controlling stem cell and differentiation.

The investigators observed that CDX2 specifically promotes changes to stem cells in the proximal colon that allow typical cell differentiation into various cell types of the colon. But loss of CDX2 function instead causes them to become more primitive and stem-cell like. Because BRAF-mutant colon cancers are associated with loss of CDX2 expression, the investigators suppressed CDX2 in cells containing the BRAF mutation to see what would happen. In proximal colon stem cells, silencing CDX2 allowed BRAF mutations to drive tumor initiation in the stem cells, whereas in the distal colon, silencing CDX2 did not yield much change. The work found that CDX2 serves important roles in regulating stem and differentiated cell states, specifically in epithelial cells lining the proximal colon.

What this means is when CDX2 function is lost, it immediately alters the state of cells to promote tumor initiation in the proximal colon, whereas in the distal colon, this doesn't happen."

Lijing Yang, M.D., lead author, oncologist at Zhongnan Hospital of Wuhan University, China

Yang was at Johns Hopkins at the time the study was conducted. "There is something very different in how stem cells are regulated in these two regions, and underscores the potential for epigenetic factors in modulating tumor initiation differently in the proximal and distal colon," Yang says.

The work has implications for new combinations of existing therapies for colon cancers, such as drugs designed to inhibit the BRAF and KRAS genes, Easwaran says."Colon cancers are very notorious in that they develop resistance to these inhibitors," he says. "There's a lot of interest in trying to figure out how else we can actually improve the efficiency of these drugs."

Next steps are to try to determine what central mechanisms are occurring in the distal colon that reduce incidence of BRAF-driven tumors, and creates a higher likelihood for KRAS-driven cancers. "Our study shows that the transcriptional states regulating stem cell and differentiation states are important for the cancer driver mutations to drive cancers," Easwaran says. "It also helps explain why tumors arising in different anatomical locations may rely on different cancer-driving mutations. Therefore, determining the mechanisms will help identify novel ways of targeting critical dependencies for these oncogenic mutations."

Study co-authors were Lijing Yang, Daniel Petkovich, Sara-Jayne Thursby, Shilpa Bisht, Yiqing Mao, Ray-Whay Chiu Yen, Tina Largent, Cynthia Zahnow, Malcolm Brock, Kathy Gabrielson and Stephen B. Baylin; and Lei Tu of Huazhong University of Science and Technology in Wuhan, China.

The work was supported by grants from the National Cancer Institute (grant numbers R01CA229240, R01CA230995, and P30CA006973 [Kimmel Cancer Center Core Grant]); the National Institute of Environmental Health Sciences (number R01ES011858); and the Evelyn Grollman Glick Scholar Award.

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Journal reference:

Yang, L., et al. (2024). Tissue-location-specific transcription programs drive tumor dependencies in colon cancer.Nature Communications. doi.org/10.1038/s41467-024-45605-4.

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Study reveals distinct molecular features of proximal and distal colon cancers - News-Medical.Net