June 29, 2020 – AffyImmune Therapeutics, Inc. disclosed novel advancements in their proprietary affinity-tuned CAR T-cell programs and technology in three presentations at the recent Annual Meeting of the American Association for Cancer Research (AACR). One presentation reported on a new CAR T design for localized and inducible cytokine release. The other two described their affinity-tuned CAR T cell design approach that maintains robust tumor cell killing while reducing toxicity. The company currently has an open IND for the treatment of relapsed or refractory thyroid cancer using an affinity-tuned CAR T-cell targeting the ICAM-1 protein, which is overexpressed in advanced thyroid cancer.
Chimeric antigen receptor (CAR)-T cell therapy has shown robust anti-cancer responses in hematologic malignancies, but applying this therapeutic approach to solid tumors has been hindered by multiple challenges, including impaired T cell infiltration of the immune-suppressive tumor environment and on-target/off-tumor cytotoxicity to normal tissues. To improve infiltration and mitigate toxicity, AffyImmune developed CARs with selective targeting and fine-tuned affinity.
Highly localized, inducible interleukin-12 release augments ICAM-1 CAR T cell activity against solid tumors
One presentation (abstract #4359) demonstrated that IL-12 secretion induced the expression of pro-inflammatory cytokines IFN-γ and TNF-α both in vitro and in vivo, suggesting a mechanism by which local release of inducible IL-12 can help overcome hostile tumor microenvironments and augment anti-tumor immune responses. The inducible IL-12 CAR T cells exhibited much more robust elimination of subcutaneous and peritoneal tumors compared to CAR T cells lacking inducible IL-12 expression.
Mitigating on-target off-tumor cytotoxicity of EpCAM CAR-T by affinity tuning
Two additional presentations focused on the multi-cancer biomarker epithelial cell adhesion molecule (EpCAM). EpCam is frequently over-expressed in a wide variety of carcinomas, including colon, gastric, pancreas, and breast cancers. This makes EpCAM attractive for targeted therapeutics, but recent clinical trials of EpCAM-targeting therapeutics have shown significant dose-limiting toxicities resulting in limited clinical responses. To selectively target EpCAM high tumors, AffyImmune is developing affinity tuned EpCAM CAR T cells.