Sensitizing solid tumors to perforin-independent CAR T-cell killing

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B163
Abstract ID: 5265

Presenting Author:
Matthew C Guttormson , Predoctoral Student at Mayo Clin. Grad. Sch. of Biomed. Sci.

Abstract:

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of blood-borne cancers, but its efficacy against solid tumors remains a challenge. While current understanding attributes tumor cell killing to perforin/granzyme-secreting cytotoxic T cells (CTLs), recent studies in our lab reveal a potential role for TNFα and IFNγ in direct tumor cell cytotoxicity. Murine melanoma cells exhibit sensitivity to cytokines produced by T-cells, particularly a combination of TNFα and IFNγ, but only at high doses. Intriguingly, dysregulation of the survival molecule Hoil-1 Interacting Protein (HOIP) in the TNFR1 signaling pathway renders initially resistant tumor cells susceptible to TNFα and IFNγ-mediated cytotoxicity. We hypothesize that inactivating HOIP will sensitize solid tumors to CAR T-cells producing TNFα and IFNγ. Proof-of-concept studies aim to demonstrate enhanced CAR T-cell therapy effectiveness against solid tumors. Success in this endeavor could suggest a promising strategy of concurrently inhibiting HOIP to augment CAR T-cell therapy for improved clinical outcomes.