On November 6, 2023 Instil Bio, Inc. ("Instil") (NASDAQ: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported two poster presentations at the SITC (Free SITC Whitepaper) 2023 Annual Meeting demonstrating that its proprietary CoStimulatory Antigen Receptor (CoStAR) platform enhances the activity of CD4+ T cells across multiple axes (Press release, Instil Bio, NOV 6, 2023, View Source [SID1234637032]).
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TIL therapy utilizes a mixed population of tumor-reactive CD4+ and CD8+ T cells, with both populations of T cells able to drive tumor regression. CoStAR has previously been demonstrated to improve proliferation, secretion of soluble factors, and in vivo tumor control in preclinical studies with mixed populations of CD4+ and CD8+ T cells. New single-cell RNA sequencing data presented at the SITC (Free SITC Whitepaper) 2023 Annual Meeting revealed enhanced gene signatures of activation and cytotoxicity in CoStAR-transduced CD4+ T cells, with significant increases in cytotoxic function of these CD4+ T cells in an in vitro cytotoxicity assay. These data suggest that CoStAR is able to endow CD4+ T cells with novel cell-killing capacity, potentially broadening the repertoire of tumor-killing TIL to include CD4+ T cells in addition to naturally cytotoxic CD8+ T cells.
Additionally, CoStAR was demonstrated to enhance the secretion of soluble factors from CD4+ T cells to boost the proliferation and survival of companion CD8+ T cells. As CoStAR provides proliferative benefit to mixed populations of CD4+ and CD8+ T cells, these data demonstrate the importance of CD4+ CoStAR-T cells in supporting the proliferation of CD8+ CoStAR-T cells through the provision of soluble factors.
"The data presented at the SITC (Free SITC Whitepaper) 2023 Annual Meeting reinforce the potential of CoStAR to broadly enhance the function of TIL therapies through multiple functional enhancements," said Bronson Crouch, CEO of Instil.
Posters may be found on the Instil Bio Publications webpage:
POSTER | SITC (Free SITC Whitepaper) ANNUAL MEETING, NOVEMBER 3-5 2023
Single cell RNA sequencing reveals functionally validated signatures of cytotoxicity in anti-FRα CoStimulatory Antigen Receptor (CoStAR) activated CD4+ T cells.
POSTER | SITC (Free SITC Whitepaper) ANNUAL MEETING, NOVEMBER 3-5 2023
Anti-folate receptor alpha (FRα) CoStimulatory Antigen Receptor (CoStAR) drives distinct cytokine-mediated proliferation responses in CD4+ and CD8+ T cells.