On April 7, 2024 Affini-T Therapeutics, Inc., a precision immunotherapy company unlocking the power of T cells against oncogenic driver mutations, reported that management is presenting data from the company’s oncogenic driver programs targeting HLA-A*11:01 KRAS G12D and HLA-A*02:01 p53 R175H at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego (Press release, Affini-T Therapeutics, APR 7, 2024, View Source [SID1234641850]). In addition, the team is presenting two trial-in-progress posters for Affini-T’s Phase 1 clinical-stage programs targeting KRAS G12V, the company-sponsored AFNT-211 study and the Fred Hutchinson Cancer Center investigator-initiated AFNT-111 study at AACR (Free AACR Whitepaper).

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"We are excited to be at AACR (Free AACR Whitepaper) unveiling new preclinical data, which includes a closer look at the promise of our novel non-viral TRAC-knocked-in T cell therapy for the treatment of p53 R175H-mutant solid tumors," said Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics. "We are also proud to present preclinical data from our cell therapy targeting KRAS G12D, which highlights the promising potential of our proprietary non-viral knock-in THRIVE platform. These findings continue to motivate our team as we advance programs leveraging TCR-engineered T cells as potential paradigm-shifting treatments for patients with solid tumor cancers."

Poster presentation details are as follows:

AFNT-212: A TRAC-knocked-in KRAS G12D-specific TCR-T cell product enhanced with CD8αβ and a chimeric cytokine receptor for treatment of solid cancers

Abstract #5973, Session: Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T
Session Date/Time: Sunday, April 7, 2024, 1:30 PM – 5:00 PM
Presenting Author: Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics
Summary: AFNT-212-engineered TCR-T cells showed high functional avidity and in vitro cytotoxicity against KRAS G12D-positive tumor cell lines, including CL40 (colon), PANC-1 and HPAF-II (pancreas), SK-LU-1 (lung), HuCCT1 (cholangiocarcinoma), etc. Additionally, engineered TCR-T cells demonstrated robust and durable anti-tumor activity in vivo and low risk of off-target/off-tumor toxicity. Affini-T’s proprietary non-viral knock-in (KI) THRIVE platform achieved high transgene integration efficiency and cell growth to yield relevant numbers of engineered TCR-T cells for clinical application. The study supports the planned clinical investigation of the novel KRAS G12D mutant TCR-engineered CD4+ and CD8+ T cell therapy in 2024.
Non-viral engineered T cell therapy specific for the hotspot mutation p53 R175H that integrates signal 1 (TCR), signal 2 (co-stimulation) and signal 3 (cytokine) and co-opts FasL-dependent apoptosis to achieve a coordinated antitumor CD4/8 T cell response

Abstract #7242, Session: Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T
Session Date/Time: Sunday, April 7, 2024, 1:30 PM – 5:00 PM
Presenting Author: Gary Shapiro, Ph.D., VP Biology Discovery, Affini-T Therapeutics
Summary: The tumor suppressor TP53 is the most frequently mutated gene across human cancers, with a highly recurrent arginine to histidine hotspot alteration in codon 175 leading to novel tumor-dependent functions. In this study, we reported the use of a novel CRISPR-Cas nuclease system to knock in a six-gene multi-cistronic cassette into the TRAC locus with high efficiency. We employed several strategies to maximize the potency and durability of a TCR-T cell product targeting the p53 R175H oncogenic driver, TCR, co-stimulation and cytokine signaling – which delivered full stimulation of both CD8+ and CD4+ T cells. These data support the planned clinical development of a novel non-viral TRAC-knocked-in T cell therapy for the treatment of p53 R175H-mutant solid tumors.