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ElevateBio and Boston Children’s Hospital to Develop iPSC-Derived Off-the-Shelf Immune Therapies

August 5, 2022

Cell and gene therapy drug developer ElevateBio has formed a new company, yet to be named, co-founded by George Daley, director of Stem Cell Transplantation at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Boston Children’s Hospital to develop allogeneic immune cell therapies based on a novel platform that generates functionally mature immune cells from induced pluripotent stem cells (iPSCs).

ElevateBio said this proprietary differentiation process overcomes the tendency of iPSCs to generate immature, embryonic blood cell types, and enables the generation of multiple subtypes of immune cells that display mature molecular signatures similar to T cells from adult blood. The peer-reviewed publication in the journal Cell Stem Cell showed that iPSC-derived mature αβ T cells exhibited antitumor activity and cytokine secretion and could serve as an ideal source for the development of allogeneic “off-the-shelf” therapies.

This is the first company to emerge from the previously announced five-year collaboration between Boston Children’s Hospital and ElevateBio to accelerate the development of novel cell and gene therapies. New company to leverage ElevateBio’s unique iPSC platform and ecosystem of enabling technologies and manufacturing capabilities to create allogeneic immune cell therapies

“CAR-T therapies have revolutionized the treatment of certain blood cancers, with complete responses in many patients undergoing this type of treatment. However, current treatment strategies involve manufacturing a customized CAR-T cell product for each individual patient, which is cumbersome and labor-intensive,” said Daley, senior author of the newly published Cell Stem Cell paper and whose lab is at Boston Children’s Hospital. “Our science offers an approach to circumvent these hurdles by offering an entirely new way of making allogeneic immune cell therapies that could pave the way for powerful treatments for a wide range of cancers.”

In the Cell Stem Cell publication, Daley’s lab at Boston Children’s Hospital described a novel differentiation process that has been shown to promote definitive hematopoiesis and supports efficient production of mature T cells. It incorporates repression of the histone methyltransferase EZH1 during iPSC differentiation to facilitate T cell maturation.

The Daley lab showed previously that EZH1 is a negative regulator of lymphoid potential during embryonic blood development. iPSC-T cells derived in a stroma-free, serum-free system following repression of EZH1, referred to as EZ-T cells, showed a molecular signature more closely resembling mature TCRαβ T cells found in adult blood. Single cell RNA sequencing showed that activated EZ-T cells give rise to high levels of memory T cells, which promotes T cell longevity and may be essential for durable remissions in cancer patients.

In vitro studies showed EZ-T cells engineered to express anti-CD19 Chimeric Antigen Receptors (CARs) exhibited cytotoxic and cytokine-producing effector functions against CD19+ lymphoid tumor cells comparable to CAR-T cells engineered from adult blood. In a xenograft mouse model injected with CD19+ diffuse large B-cell lymphoma (DLBCL) cells, EZ-T cells expressing anti-CD19 CARs demonstrated increased anti-tumor activity versus traditional iPSC-T cells generated without EZH1 knockdown.

Author: Rare Daily Staff

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