New data demonstrates Umoja’s synthetic receptor enabled differentiation (ShRED™) as a novel platform to differentiate and expand progenitor cells and cytotoxic innate lymphocytes using the RACR™ synthetic cytokine receptor system
Umoja’s RACR-driven ShRED platform addresses multiple iPSC-derived immune cell manufacturing challenges through reducing requirements for complex raw materials and improved yields of progenitors and final product
SEATTLE, July 28, 2022 – Umoja Biopharma, Inc., an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells in vivo to treat patients with solid and hematologic malignancies, announced new data at the 2022 iPSC Manufacturing Summit held in Boston, Mass. on the development of a precision genome engineered induced pluripotent stem cells (iPSCs) to incorporate a synthetic cytokine receptor, permitting more efficient differentiation and expansion of cells into functional, persistent cytotoxic cell types that is further compatible with efficient scale-up production.
“Our newest data highlights a new way to efficiently differentiate and expand high-quality iPSCs in quantities necessary for treating more patients with potentially life-changing cell therapies,” said lead author of the study and principal scientist at Umoja, Teisha Rowland, Ph.D. “Previously, scientists were limited with culturing these cells on plates, but with the new ShRED system we show that it is possible to grow cells in suspension, which is expected to translate to large-scale manufacturing. Importantly, we also showed that CAR-NK cells made using this new technique are highly functional therapeutic cells. This further validates employing our RACR technology platform to overcome critical limitations facing the cell therapy industry.”
On Thursday July 28th, Principal Scientist Teisha Rowland, Ph.D., gave a presentation titled “Engineering iPSCs with Synthetic Receptors to Drive Differentiation Compatible with Scale-Up.” The presentation demonstrated progress on Umoja’s iPSC platform and the development of a synthetic receptor enabled differentiation (ShRED) protocol that employs a rapamycin activated cytokine receptor (RACR™) to drive differentiation and expansion of iPSCs in a controlled and consistent manner, without the addition of expensive growth factors and cytokines. Activating RACR with a rapamycin analog (rapalog) during hematopoietic progenitor (HP) generation was shown to increase HP yield controls in conventional cell culture format. Additional improvement of cell culture conditions further enhanced RACR-driven yields.
Furthermore, resultant iPSC-derived cytotoxic innate lymphocytes (RACR-iCILs) displayed improved innate cytotoxicity and serial killing in several tumor models. CAR-RACR-iCILs (cells engineered with chimeric antigen receptors) displayed potent and specific CAR-driven and innate tumor killing. Furthermore, RACR engineered NK cells demonstrated enhanced tumor control in a mouse breast cancer model. In addition, RACR-iCIL cells can be produced with high yields when grown in suspension, eliminating requirements for 2D culture that limit scale up manufacture of iPSC derived cell therapy products.
“We are continuing to advance our “off-the-shelf” iPSC therapy platform that aims to overcome major challenges in allogeneic cell therapy, including eliminating the need for toxic lymphodepletion and reducing manufacturing complexity and cost,” said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. “We are excited to share this new data on the development of our ShRED platform for the differentiation and expansion of iPSC-derived cells which is expected to yield a more consistent and potent product. The continued progress across our four complimentary platforms truly exemplifies Umoja’s commitment and determination towards developing curative treatments that can be delivered to any patient, with any tumor, at any time.”
CAR T cells generated by the body with VivoVec can be expanded and sustained with the rapamycin activated cytokine receptor (RACR) system, an engineered signaling system designed to improve chimeric antigen receptor (CAR) T cell persistence and produce durable anti-tumor responses. The RACR/CAR payload is integrated into the genomic DNA of a patient’s T cells. Rapamycin activates the RACR system resulting in preferential expansion and survival of cancer-fighting T cells. The RACR technology enables a patient’s cells to expand in a manner that resembles a natural immune response that does not require lymphodepletion, promoting durable T cell engraftment. RACR/CAR technology can also be used to enhance ex vivo manufacturing in support of more traditional autologous or allogeneic cell therapy manufacturing processes. To learn more about Umoja’s RACR platform please visit https://www.umoja-biopharma.com/platforms/
About Umoja Biopharma
Umoja Biopharma, Inc. is an early clinical-stage company advancing an entirely new approach to immunotherapy. Umoja Biopharma, Inc. is a transformative multi-platform immuno-oncology company founded with the goal of creating curative treatments for solid and hematological malignancies by reprogramming immune cells in vivo to target and fight cancer. Founded based on pioneering work performed at Seattle Children’s Research Institute and Purdue University, Umoja’s novel approach is powered by integrated cellular immunotherapy technologies including the VivoVec in vivo delivery platform, the RACR/CAR in vivo cell expansion/control platform, and the TumorTag targeting platform. Designed from the ground up to work together, these platforms are being developed to create and harness a powerful immune response in the body to directly, safely, and controllably attack cancer. Umoja believes that its approach can provide broader access to the most advanced immunotherapies and enable more patients to live better, fuller lives. To learn more, visit http://umoja-biopharma.com/.
Darren Opland, Ph.D.