On November 3, 2023 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company focused on innovative gamma-delta T cell therapies, reported new positive preclinical data from its induced pluripotent stem cell (iPSC) gamma-delta T cell platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting (Abstract #: 637 in Exhibit Halls A and B1) (Press release, In8bio, NOV 3, 2023, View Source [SID1234636885]). The data represents a significant advance in the development of the INB-500 iPSC program towards the development of allogeneic gamma-delta T cell therapies.
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"Our deep understanding of gamma-delta T cell biology allows for significant ex vivo expansion capabilities," said William Ho, Co-founder and CEO. "We have successfully developed and utilized a robust serum and feeder-free process for generating iPSC derived gamma-delta T cells, representing an important step towards developing a truly allogeneic ‘off-the-shelf’ gamma-delta T cell source for therapeutic development."
The presented data underscores the platform’s ability to reprogram donor cells into iPSCs, expand them, and guide their differentiation into gamma-delta T cells through IN8bio’s proprietary process, which can be scaled for full GMP manufacturing. Notably, the platform enables the differentiation into both Vd1+ and Vd2+ cell subtypes using cell-type specific processes. The iPSC-derived gamma-delta T cells underwent comprehensive characterization, encompassing morphological analysis, cell surface markers and functional assessment via tumor cell killing assays. Key findings include:
iVd1+ gamma-delta T cells expressed the cell markers expected of innate gamma-delta T cells, including a strong capacity for cytokine release, indicating that the cells possess an effector phenotype.
To date, hundreds of millions of iVd1+ gamma-delta T cells have been produced from single iPSC clones at a low passage number.
The cells demonstrated robust cytotoxic activity across a variety of cancer cell lines, including ovarian, glioblastoma (GBM), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cell lines, potentially providing an allogeneic platform for a broad range of cancers.
Cryopreservation did not impact the cells with the Vd1+ gamma-delta T cells showing comparable cytotoxicity to fresh cells, which allows them to be expanded and banked for potential on-demand clinical use.
"High concentrations of gamma-delta T cells in both peripheral blood and in solid tumor infiltrates are associated with improved survival outcomes in both hematopoietic and solid cancers," said Lawrence Lamb, PhD, Co-founder and Chief Scientific Officer. "iPSC-derived gamma-delta cells could address existing challenges, including donor sourcing and limitations of sufficient cell numbers to sustain a therapeutic effect particularly in solid tumors. iPSCs, with their nearly unlimited self-renewal capacity, multi-lineage differentiation potential, and relative ease of generic engineering offer the possibility of therapeutic cell production for patients across a wide range of cancers."