Therapeutic cancer vaccines: Are we there yet?

Christopher A. Klebanoff, Nicolas Acquavella, Zhiya Yu, Nicholas P. Restifo

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

Summary: Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer-based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront: (i) a corrupted tumor microenvironment containing regulatory T cells and aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor targets capable of antigen loss and immune evasion. Future progress may come from innovations in the development of selective preparative regimens that eliminate or neutralize suppressive cellular populations, more effective immunologic adjuvants, and further refinement of agents capable of antagonizing immune check-point blockade pathways.

Original languageEnglish (US)
Pages (from-to)27-44
Number of pages18
JournalImmunological Reviews
Volume239
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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Keywords

  • Cell intrinsic modulators of metabolism and memory formation
  • CTLA-4
  • mTOR
  • PD-1
  • Toll-like receptor agonist
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Klebanoff, C. A., Acquavella, N., Yu, Z., & Restifo, N. P. (2011). Therapeutic cancer vaccines: Are we there yet? Immunological Reviews, 239(1), 27-44. https://doi.org/10.1111/j.1600-065X.2010.00979.x