Combination of a novel TCR Vβ chain-directed selective T cell activator with standard of care therapy for head and neck cancer improves antitumor responses and promotes regression of checkpoint-refractory tumor models.

backgroundImmune checkpoint blockade (ICB) treatment, alone or in combination with standard anticancer therapies, has led to important progress in the treatment of head and neck squamous cell carcinoma (HNSCC). Yet, a significant proportion of patients with carcinogen-associated HNSCC (human papillomavirus (HPV)

methodsC57BL/6 mice bearing MOC1 or MOC2 tumors were treated weekly with mSTAR1302, cisplatin, and α-programmed cell death protein 1 (PD-1) antibody to determine antitumor efficacy and survival benefit. Immune populations and their effector functions were characterized by flow cytometry and cytokine assays. The tumor microenvironment's immune architecture was analyzed by multiplex immunofluorescence. Gene expression analysis was conducted to gain an understanding of the mechanism of action of the combination therapy.

resultsCombination therapy with mSTAR1302, cisplatin, and α-PD-1 promoted robust antitumor activity, higher numbers of mice with complete resolution of tumors, and significantly prolonged survival compared with mSTAR1302 monotherapy or SOC treatment in MOC1 and MOC2 tumors. Tumor-free animals from cohorts treated with the combination therapy demonstrated protection against tumor rechallenge and an overall increase in antigen-specific T cells. Tumor growth inhibition was associated with the expansion of Vβ13 CD8

conclusionThese findings provide a rationale for the combination of STAR0602 and SOC therapy in the clinical setting for patients with recurrent or metastatic HPV