The University of Texas MD Anderson Cancer Center has partnered with Takeda Pharmaceutical on immuno-oncology therapies. Specifically, they announced an exclusive license deal and research agreement to develop cord-blood derived chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies. They say these CAR-NK therapies will be armored with IL-15 to treat B-cell and other cancers.
Under the deal, Takeda will access MD Andersons CAR-NK technology platform and pick up the exclusive rights to develop and commercialize up to four programs. Those programs include a CD19-targeted CAR-NK-cell therapy and a B-cell maturation antigen (BCMA)-targeted CAR-NK therapy. They will collaborate on research to advance the programs.
Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient settingenabling more patients to be treated effectively, quickly and with minimal toxicities, said Katy Rezvani, professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments.
MD Andersons allogeneic CAR NK technology platform collects umbilical cord blood, isolates NK cells for it, and then engineers those NK cells to express CARs against specific cancer targets. They utilize a retroviral vector to deliver genes to the CAR NK cells, which both improves their effectiveness and fine-tunes them for specific cancer cells. The CD19 CAR makes the cells even more specific for B-cell malignancies, and the IL-15 improves the proliferation and survival of the CAR-NK cells in the body.
Currently approved CAR-T therapies, which essentially means Novartis Kymriah (tisagenlecleucel) and Gilead Sciences Yescarta (axicabtagene ciloleucel), isolate T-cells from the patients blood, which are then engineered to express CARs against the patients specific cancer. The downside to this is that it is time-consuming, taking several weeks. So this approach, which others are also working to develop, would be more of a one-size-fits-all therapy that could be used to treat the patient immediately rather than uniquely engineer the CARs.
MD Anderson and Takeda expect their CD19 CAR NK therapy could be administered in an outpatient setting. There is an ongoing Phase I/IIa trial in patients with relapsed and refractory B-cell cancers. In it, there has been little or no evidence of the severe cytokine release syndrome (CRS) or neurotoxicity associated with Kymriah and Yescartaalthough those companies and the affiliated healthcare practitioners have developed protocols for minimizing those effects.
As well as developing the CAR NK-cell therapies, Takeda and its partners are working to improve the safety, efficacy and accessibility of the first-generation CAR-Ts, including gamma delta CAR-Ts, induced pluripotent stem cell-derived CAR-Ts, CAR-Ts that target solid tumors, and other approaches.
Takeda reportedly hopes to advance five oncology cell therapies into the clinic by the end of fiscal year 2020.
Under the agreement, Takeda will handle development, manufacturing and commercialization of CAR-NK products that come out of the partnership. MD Anderson will receive an undisclosed upfront payment and be eligible for various milestones for each target in addition to tiered royalties on net sales of any products that come out of the deal.
MD Andersons CAR-NK platform is led by Rezvani and supported by the adoptive cell therapy platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, which are all part of MD Andersons Moon Shots Program.
MD Andersons CAR-NK platform represents the curative potential of cell therapies, which is why we are establishing the CD19 CAR NK as our lead cell therapy candidate in oncology, said Andy Plump, president of Research and Development at Takeda. We need to work swiftly and with purpose, and as such, we intend to initiate a pivotal study of the CD19 CAR NK in 2021.