While cancer vaccines are in the clinic, several issues remain to be addressed to increase vaccine efficacy.
In particular, whether, how and how frequently a patient should be boosted remains to be defined. Here we have assessed the ability of dendritic cell (DC)-based vaccines to induce a long-lasting tumor-specific cytotoxic T lymphocyte (CTL) response in either prophylactic or therapeutic settings by taking advantage of transplantable and spontaneous mouse tumor models. Implementing a 24h ex vivo intracellular cytokine production assay, we have found that priming with a DC-based vaccine induced a long-lasting CTL response in wild type mice, and homologous boosting better sustained the pool of central memory T cells, which associated with potent protection against B16F1 melanoma challenge. Appropriate timing of booster vaccination was also critical, as a tight boosting schedule hindered persistence of IFNγ-competent memory CD8+ T cells and mice survival in prophylactic settings. Conversely, prime/boost vaccination proved to be of no advantage or even detrimental in therapeutic settings in B16F1 and transgenic adenocarcinoma of the mouse prostate (TRAMP) models, respectively. While DC-priming was indeed needed for tumor shrinkage, restoration of immune competence and prolonged survival of TRAMP mice, repeated boosting did not sustain the pool of central memory CTLs, and was detrimental for mice overall survival. Thus, our results indicate that booster vaccinations impact on anti-tumor immunity to different extents depending on their prophylactic or therapeutic administration, and suggest evaluating the need for boosting in any given cancer patient depending on the state of the disease.
Written by:
Ricupito A, Grioni M, Calcinotto A, Hess Michelini R, Longhi R, Mondino A, Bellone M. Are you the author?
Immunology, Gene Therapy and Bio-Immunotherapy of Cancer, Istituto Scientifico San Raffaele.
Reference: Cancer Res. 2013 Mar 28. Epub ahead of print.
doi: 10.1158/0008-5472.CAN-12-2449
PubMed Abstract
PMID: 23539449
