SBIR INNOVATIVE CONCEPT AWARD - DETECTION, DIAGNOSIS, TREATMENT, PREVENTION AND RESEARCH OF PEDIATRIC CANCERS AND/OR RARE CANCERS

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Immunotherapies harness the body’s own natural defenses to fight cancer and can lead to durable responses in some patients, but clinical benefit has remained limited. Therapeutic vaccines derived from whole tumor lysates are a promising treatment strategy that ares well tolerated and have shown promising results in early clinical trials, stimulating neoantigen-specific immune responses in a subset of patients. Yet the majority of patients are poorly responsive to vaccine treatment, underscoring the need to devise improved strategies for stimulating anti-tumor activity, and thereby preventing tumor escape. To induce robust cellular immunity against esophageal cancer, a rare but particularly aggressive malignancy that leads to significant morbidity and mortality in the US, our strategy is to optimally prime neoantigen-reactive T cells from individual patients with esophageal cancer. We propose an innovative priming method to induce neoantigens in tumor cells prior to lysate generation, thereby enhancing the immunogenicity of each vaccine preparation, and test efficacy and specificity in vitro. Finally, we will test in vivo efficacy of our therapeutic preparation using a mouse model of esophageal cancer. Our goal is to advance novel approaches to effectively mobilize anti-tumor immunity, improve therapeutic vaccine efficacy and overcome immunotherapeutic resistance in esophageal cancer.