AffyImmune Therapeutics presents novel CAR T development programs at the annual meeting of the American Association of Cancer Research
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- Published on Friday, 03 July 2020 10:25
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NATICK, MA, USA I July 2, 2020 I 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.
In one EpCAM presentation (abstract #4534), author Huan Yang of AffyImmune described the development of AffyImmune's EpCAM targeting technology, which involved a rational design approach incorporating lower-affinity single-chain antibody (scFv) variants. While high-affinity EpCAM-targeting CAR T-cells kill both normal human epithelial cells as well as EpCAM-high tumor cells, AffyImmune's lower affinity CAR T-cells were shown to spare normal human epithelial cells while still effectively killing tumor cells expressing high levels of EpCAM. Further, transcriptional profiling suggested that lower affinity CAR T variants were less prone to exhaustion.
Eradication of EpCAM expressing solid tumors by low-affinity CAR T cells
In the final, complimentary presentation (abstract #4534), it was shown that potent in vivo anti-tumor activity could be obtained using lower affinity CAR T cells in an intraperitoneal gastric cancer model, an orthotopic pancreatic tumor model, and in a PDX model using a gastric cancer patient-derived xenograft. The authors concluded that the technology enabled "eradication of various difficult-to-treat solid tumors, without triggering severe treatment-related toxicities," showing promise for the fine-tuning approach as a general strategy for identifying a therapeutic window for CAR-T cells in challenging, solid tumor types.
"Together, these presentations demonstrate the elegance and effectiveness of AffyImmune's strategy," said AffyImmune co-founder Moonsoo Jin. "We're focused on identifying the optimal affinity for targeting tumor-associated antigens using CAR T-cells. In this way, it is possible to both avoid non-tumor cells expressing basal levels of the target and to optimize CAR T-cell function, longevity, and tumor killing."
All presentations were presented at the AACR Virtual Annual Meeting II between June 22-24, 2020, and are available for on-demand viewing.
About AffyImmune Therapeutics, Inc.
AffyImmune is realizing the potential of cancer immunotherapy by extending the anti-cancer activity of CAR-T cell therapy to solid tumors, improving the safety and efficacy of CAR-T treatment. Based on Professor Moonsoo Jin's work at Weill Cornell Medicine, AffyImmune's proprietary technology allows fine-tuning of CAR-T cells affinity to selectively kill tumor cells, reducing toxicity. AffyImmune scientists have also developed a tracking system, that can be engineered into any CAR-T cell, to allow for real-time localization of cells after administration to patients.
AffyImmune's lead asset, AIC100, is an affinity-tuned, 3rd generation CAR-T cell therapy co-expressing SSTR2. Preclinical studies in various solid tumor models demonstrated AIC100's robust and enduring tumor eradication and superior safety profile compared to standard, high-affinity CAR T cell therapy. In 2019, AffyImmune received Orphan Drug Designation by the FDA for AIC100 and began recruitment for a Phase 1 trial to treat advanced thyroid cancer.
Founded in 2016, AffyImmune is headquartered in Natick, MA, and is incubated by ORI Capital.
About ORI Healthcare Fund L.P.
ORI Healthcare Fund is a $200 million venture capital fund focused on investing in innovative companies with disruptive technologies in the healthcare industry globally. The General Partner of the Fund was founded by Ms. Simone (Hong Fang) Song, the former head of China Healthcare Investment Banking at Goldman Sachs.
SOURCE: AffyImmune Therapeutics