Background: The current precising T cell therapy focused on targeting tumor antigens, but these T-cell therapies are limited by its inability to penetrate the collagen barrier surrounding tumors and addressing the heterogeneity challenges of tumors. Here we present a novel type of T cell therapy—cell surface vimentin (CSV)–targeted and membrane-anchored IL12-armed (attIL12) T cells for reducing collagen production in tumors.
Objective: Our goal for this presentation is to share a novel type of T cell therapy that can disrupt collagen production of both tumor cells and CAFs to boost TIL penetration and improve efficacy as well as safety.
Design/Methods: We have used our proprietary attIL12 to arm autologous tumor derived T cells (not tumor specific) and TILs and test collagen disruptions/efficacy in PDX tumors; we have also used immune competent mice and attIL12-ova-targeted mouse TILs to evaluate the safety and the antigen spreading. Clinical Trials were launched.
Results: In this presentation, we will report that tumor collagens are derived from both CAFs and tumor cells. We discovered that attIL12-T cells can reduce collagen production from CAFs but not from tumor cells. While attIL12-TILs can reduce collagen production from both. Interestingly, CCKAR directly boosts collagen production by tumor cells in vitro and in vivo. This disruption of collagen production by tumor cells by attIL12-TILs overcomes resistance to attIL12-T cell treatment and required a simultaneous interaction between the CSV on autologous tumor cells, which is targeted by attIL12, and HLA-TCR on attIL12-TILs; when either interaction was abrogated, collagen production and CCKAR expression were not shut down. Thus, this attIL12-TIL therapy holds great clinical potential for boosting T-cell infiltration in high-grade, collagen-rich tumors.
Conclusions: Our early stage attIL12-T cell therapy trial has shown promising in boosting T cell penetration and attIL12-TIL trial has been launched.