P53MVA therapy in patients with refractory gastrointestinal malignancies elevates p53-specific CD8+ T-cell responses.

ABSTRACT:

Purpose

To conduct a phase I trial of a modified vaccinia Ankara (MVA) vaccine delivering wild-type human p53 (p53MVA) in patients with refractory gastrointestinal cancers.

Experimental design

Three patients were vaccinated with 1.0×10(8) plaque-forming unit (pfu) p53MVA followed by nine patients at 5.6×10(8) pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre- and post-immunization for immunophenotyping, monitoring of p53MVA-induced immune response, and examination of PD1 checkpoint inhibition in vitro.

Results

p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. CD4+ and CD8+ T cells showing enhanced recognition of a p53

SUBMITTER: Hardwick NR 

PROVIDER: S-EPMC4155000 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature