JPM points to KRAS and p53 mutations driving cancer, new TCR cell therapy debuts

▎WuXi AppTec Content Team Editor A few days ago, Affini-T, a cutting-edge company that debuted at the JPM conference, introduced its innovative cell therapy technology platform and R&D pipeline
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Affini-T was co-founded by scientists at the Fred Hutchinson Cancer Center in the United States to use synthetic biology and gene editing to develop a new generation of T cell receptor (TCR) cell therapies targeting cancer driver mutations
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The company's R&D strategy is to target cancers driven by mutations in specific oncogenes, such as those driven by mutations in the KRAS gene, to discover specific TCRs already present in humans
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These TCRs are able to discriminate between KRAS mutants and wild-type KRAS, providing selectivity for TCR cell therapy
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▲The company has discovered selective TCRs for KRAS G12V and KRAS G12D (Image source: Affini-T's official website) Affini-T's cell therapy design not only expresses TCR targeting oncogenic mutation targets in CD4-positive and CD8-positive T cells TCR, but also expresses a CD8 co-receptor
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The CD8 co-receptor enhances TCR binding to its target
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CD4-positive T cells expressing TCR and CD8 co-receptors can not only produce cytotoxic responses to tumor cells, but also enhance the function of CD8-positive T cells
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In addition, CD4-positive T cells can also interact with dendritic cells to stimulate the secretion of IL-12, induce the production of inflammatory signals, and stimulate more anticancer immune cell responses
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Image source: Affini-T's official website In order to improve the survival and function of T cells in the tumor microenvironment (TME) with immunosuppressive functions, the company has also developed a new chimeric receptor called switch
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For example, a switch receptor replaces the intracellular domain of the Fas receptor, which originally mediates cell death signals, with 4-1BB, which promotes cell survival, so that the signal that originally caused T cell death instead promotes cell survival.
In pancreatic cancer models has been shown to significantly prolong animal survival
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Image source: Affini-T's official website The company's R&D pipeline includes candidate TCR cell therapies targeting KRAS G12V and KRAS G12D mutants, as well as p53 mutants
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Investigational therapies for virus-driven cancers are already in clinical development
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The company says its goal is to use cutting-edge engineering and synthetic biology tools to optimize T-cell function and rewrite the rules of the solid tumor microenvironment to bring lasting clinical remissions to patients
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Reference: [1] Unlocking the power of T cells against oncogenic driver mutations.
Retrieved January 14, 2022, from https:// Deck-2022-Sent.
pdf[2] New Cell Therapy Player Makes Public Debut at JPM.
Retrieved January 14, 2022, from https:// -makes-public-debut-at-jp-morgan-healthcare-conference/Disclaimer: The WuXi AppTec content team focuses on introducing global biomedical health research progress
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