Vacunas para el tratamiento del Cáncer

Cancer Vaccine Field Remains Lively Despite Setbacks: 10+ Agents in Advanced Testing
Andrew D. Smith
Published Online: Tuesday, February 10, 2015
Philip W.Kantoff, MD


The only therapeutic cancer vaccine ever to win approval from the FDA has repeatedly missed sales projections, plunging the company that developed it into bankruptcy proceedings.

Every other vaccine to make it through phase III trials thus far has failed to reach statistically significant benchmarks for documenting therapeutic benefit. Indeed, just last year, two major pharmaceutical companies announced that once-promising therapeutic cancer vaccines had faltered in costly late-stage trials.

Yet researchers and investors alike remain cautiously optimistic about the potential for therapeutic anticancer vaccines.

At least 10 vaccine candidates have entered advanced testing phases on the strength of impressive early-stage results (Table). Notably, the FDA is reviewing an application for the oncolytic immunotherapy agent talimogene laherparepvec (TVEC) for the treatment of patients with regionally or distantly metastatic melanoma, with a decision expected by October 27, 2015. In addition, the agency has granted breakthrough therapy status to the combination of the vaccines CRS-207 and GVAX Pancreas in metastatic pancreatic cancer. In research circles, the belief that vaccines may work better in combination with other treatments than they do as monotherapies has stimulated a new line of study.

“Sipuleucel-T [Provenge] has failed from a financial point of view so far, but its monetary struggles haven’t diminished interest in cancer vaccines,” said Philip W.Kantoff, MD, a Harvard Medical School professor who heads the Department of Solid Tumor Oncology at Dana-Farber Cancer Institute.

“To the contrary, its very existence has stimulated research and trials because it is proof positive that a long-held concept can produce realworld benefits. It is a building block, and there are a number of experimental vaccines out there that may take the next step,” said Kantoff. Kantoff helped lead the clinical trial1 that prompted the FDA to approve sipuleucel-T in 2010 as monotherapy for asymptomatic or minimally symptomatic metastatic castrateresistant prostate cancer. Despite the excitement that accompanied the drug’s launch, Dendreon Corporation has not been able to translate the pioneering autologous dendritic cell vaccine into commercial success and filed a voluntary bankruptcy petition in November 2014.

Therapeutic cancer vaccines currently in development fall into four main categories, depending upon the strategy employed, according to the Society for the Immunotherapy of Cancer. These approaches include autologous tumor cell vaccines, peptide vaccines, dendritic or antigen-presenting cell vaccines, and vector-based vaccines.

Currently, Kantoff is helping to conduct a phase III trial for another vaccine candidate that researchers have been watching: the prostate cancer vaccine PROSTVAC. The experimental treatment uses seven injections spaced across 5 months to stimulate an immune response against prostate specific antigen (PSA). The initial priming dose combines a modified version of Vaccinia with PSA and three molecules designed to stimulate the immune system: LFA-3, ICAM-1, and B7.1. The six booster shots pack the same mix of PSA and immune system stimulants into a modified fowlpox vaccine.

Trials to date have deployed the experimental vaccine regimen after tumors have become resistant to chemical castration and started to metastasize, but before the patients have been treated with chemotherapy.

Such tumors typically respond poorly to most treatments, but early-stage PROSTVAC trials have succeeded. The treatment has at least doubled PSA-specific T-cells in more than half of all trial patients and extended overall survival by an average of 8.5 months.2

“Nothing guarantees success in phase III trials, but those numbers certainly constitute compelling preliminary data, and they come from monotherapy trials that may not play to the vaccine’s real strength,” said James L. Gulley, MD, PhD