Abstract 2882: p53MVA therapy in patients with refractory gastrointestinal malignancies primes robust CD8+ T cell responses

Abstract

Abstract PURPOSE: To conduct a Phase I safety trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in patients with refractory gastrointestinal malignancies. EXPERIMENTAL DESIGN: Three patients were vaccinated with 108 pfu p53MVA followed by nine patients at 5.6 x 108 pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre vaccine and post vaccination for immunophenotyping and assessment of p53MVA induced immune response. RESULTS: p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. Induction of strong T cell and antibody responses to the MVA backbone were apparent. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T cell compartment (p=0.03). However in most patients this did not expand further with the second and third immunization. Some patients exhibited a decline in myeloid-derived suppressor cells post vaccine, but this was not statistically significant. The frequency of PD-1+ T cells detectable in patients PBMC was significantly higher than healthy controls. Furthermore, the frequency of PD-1+ CD8+ T cells showed an inverse correlation with the peak CD8+ T cell response to p53 (p=0.02). CONCLUSION: p53MVA was well tolerated and induced robust CD8+ T cell responses. Combination of p53MVA with immune checkpoint inhibition could improve sustained immune responses and lead to clinical benefit. Citation Format: Nicola Hardwick, Mary Carroll, Teodora Kaltcheva, Dajun Qian, Jonathan Espenschied, Lucille Leong, Peiguo Chu, Joseph Kim, Joseph Chao, Marwan Fakih, Joshua Ellenhorn, Don Diamond, Vincent Chung. p53MVA therapy in patients with refractory gastrointestinal malignancies primes robust CD8+ T cell responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2882. doi:10.1158/1538-7445.AM2014-2882