Personalized Tumor Membrane Vesicle Vaccine Immunotherapy for Head and Neck Squamous Cell Carcinoma (HNSCC) 2253480

Abstract Introduction Head and neck cancer exhibits a high degree of heterogeneity, with lack of common therapeutic targets. We have developed an autologous therapeutic cancer vaccine approach using tumor-membrane vesicles (TMVs) prepared from surgically removed tumor tissue incorporated with glycolipid-anchored immunostimulatory molecules with B7.1 and IL-12. We hypothesize that tumors resistant to immune checkpoint inhibitor therapy (cold tumors) will be turned into hot tumor by TMV vaccine and induce response to anti-PD-1 antibody therapy in advanced metastatic HNSCC patients. Our phase 1 clinical trial (NCT06868433) will evaluate a novel personalized immunotherapy approach using TMV prepared from the patients’ own surgically excised tumor tissue and modifying them by attaching GPI-B7-1 and GPI-IL-12 as immune boosting molecules. Methods A total of 10 HNSCC tumor specimens were collected (0.29-1.23 grams) and graded for cellularity by a pathologist. Tumor samples were then homogenized, and homogenate was ultracentrifuged over a sucrose gradient to enrich TMV. TMV preparations were incorporated with GPI-B7-1 and GPI-IL-12 to generate the TMV vaccine. We used established murine oral cancer models to investigate the protective anti-tumor immune response of TMV vaccine in combination with anti-PD1 antibody therapy. Spleens were flash frozen in liquid nitrogen and stored in -80oC for RNA-seq analysis. Results TMV yields were 2.5 — 5 mg/gram of tissue from patient samples. Further refinement of the TMV production process yielded up to 6 mg of TMV/gram of tumor. We have just begun enrolling patients in the phase 1 trial and banking tumor for vaccine production if they ever become eligible to receive the vaccine to treat recurrent/metastatic disease. RNA-seq data from mouse model suggests that the TMV vaccine showed synergistic activity when combined with anti-PD1 antibody, with enhanced T cell responses. Conclusion TMV vaccine synergizes with anti-PD1 in inducing anti-tumor responses. Funding Source Supported by NIH/NCI 1R01CA262123-01A1 to DMS & PS. Topic Categories Vaccines and Immunotherapy (VAC)