Project 4

A Phase I study of a p53-MVA vaccine for advanced colon, gastric and pancreatic cancer

Despite recent advances in targeted therapies, the outlook for patients with advanced GI cancer remains bleak, and new treatments are urgently needed. Cancer vaccines have potential to improve outcomes for cancer patients and are being actively developed. The p53 protein is a well-characterized suppressor of uncontrolled cell division. Mutations in the gene occur in ≥50% of all patients with solid tumors, whereby it acquires oncogenic properties, and leads to high levels of dysfunctional p53 protein within malignant cells. The concentration of normal, non-mutant p53 in healthy cells is low, making p53 an attractive target for selective killing of tumor cells. Our preclinical studies have shown that immunization of mice with p53-MVA vaccine causes rejection of established tumors and generation of systemic tumor immunity.  In addition, p53-MVA was used to generate cytotoxic T cells from the blood of cancer patients that are capable of killing tumor cells. Recombinant MVA vaccines have an impressive safety record, being administered in numerous clinical trials with only mild side-effects. Along with a medical oncologist, we have initiated a first in human, Phase 1 dose-escalation study evaluating the safety and immunogenicity of clinical grade p53-MVA vaccine in patients with gastric, colon and pancreatic cancers. The first 3 patients have already completed a course of vaccination with low dose p53-MVA. As no severe toxicities have been observed, the next group of 4 patients received a higher dose of p53-MVA which is more likely to produce clinical effects. CT scans were used to evaluate progression of disease and blood draws were taken for safety and immunological assessments throughout the vaccination phase. A Phase 2 clinical trial will involve p53-MVA vaccination early after diagnosis, when beneficial outcomes are more attainable. In this clinical trial, the p53MVA vaccine will be given concurrently with the standard chemotherapy drug gemcitabine, with the aim of extending survival. These studies will greatly advance our vaccine program for patients with GI cancer who currently have few alternatives.
 
Personnel
Vincent Chung, MD
Staff Physician, Department of Medical Oncology & Therapeutics Research
Enrolls and consents patients

Nicola Hardwick, PhD
Post-Doctoral Fellow, Division of Translational Vaccine Research
Conducts the laboratory investigations
 
Department of Medical Oncology Staff Physicians
Enrolls and consents patients
 
Read the study abstract.