A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma

SIMPLE SUMMARY: We investigated the feasibility and immunogenicity of an autologous Dendritic Cell (DC) vaccine pulsed with peptide neoantigens in combination with a standard of care regimen. The vaccine program took place in a serous endometrial mismatch repair (MMR) deficiency setting. We demonstrate for the first time the feasibility of producing a peptide DC vaccine in endometrial carcinoma. The safety and immunogenicity of this personalized vaccine was demonstrated by the detection of polyfunctional and durable T-cell responses. ABSTRACT: Endometrial cancer (EC) is a common gynecological malignancy and the fourth most common malignancy in European and North American women. Amongst EC, the advanced serous, p53-mutated, and pMMR subtypes have the highest risk of relapse despite optimal standard of care therapy. At present, there is no standard of care maintenance treatment to prevent relapse among these high-risk patients. Vaccines are a form of immunotherapy that can potentially increase the immunogenicity of pMMR, serous, and p53-mutated tumors to render them responsive to check point inhibitor-based immunotherapy. We demonstrate, for the first time, the feasibility of generating a personalized dendritic cell vaccine pulsed with peptide neoantigens in a patient with pMMR, p53-mutated, and serous endometrial adenocarcinoma (SEC). The personalized vaccine was administered in combination with systemic chemotherapy to treat an inoperable metastatic recurrence. This treatment association demonstrated the safety and immunogenicity of the personalized dendritic cell vaccine. Interestingly, a complete oncological response was obtained with respect to both radiological assessment and the tumor marker CA-125.