Induction of p53-specific immune responses in colorectal cancer patients receiving a recombinant ALVAC-p53 candidate vaccine.

摘要: Purpose: The tumor-associated auto-antigen p53 is commonly overexpressed in various types of human cancer, including colorectal cancer. Experiments preclinical models have shown that it can serve as a target for T-cell-mediated tumor-eradication. feasibility p53-specific therapeutic vaccination was investigated cancer patients. Experimental Design: A Phase I/II dose-escalation study performed evaluated the effect recombinant canarypoxvirus (ALVAC) vaccine encoding wild-type 15 patients with advanced Each group five received three i.v. doses one-tenth dose, one-third or 1 dose [1 = × 10 7.5 cell culture infectious dosis (CCID) 50 ]. Results: Potent T-cell and IgG antibody responses against vector component ALVAC were induced majority Enzyme-linked immunosorbent-spot assay (ELISPOT) analysis vaccine-induced immunity revealed presence IFN-γ-secreting T cells both p53, whereas no significant interleukin-4 detected. Vaccine-mediated enhancement found two highest-vaccine-dose group. Conclusions: This demonstrated feasibility, even to elicit immune ubiquitously expressed p53. Our results form basis additional studies will explore antitumor capacity containing multivalent vaccines limited tumor burden.