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PMID: 21198663 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Therapeutic cancer vaccines: are we there yet?

Immunological reviews ·Vol. 239 ·No. 1 ·2011-01-00 ·Pages 27-44

Klebanoff CA, Acquavella N, Yu Z, Restifo NP

Abstract

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.

MeSH Terms
Adjuvants, Immunologic Adoptive Transfer Antigens, Differentiation, T-Lymphocyte/immunology Antigens, Neoplasm/immunology Cancer Vaccines/immunology,therapeutic use Humans Immunotherapy Neoplasms/immunology,therapy Randomized Controlled Trials as Topic T-Lymphocyte Subsets/immunology Toll-Like Receptors/agonists Treatment Outcome
Chemicals
Adjuvants, Immunologic Antigens, Differentiation, T-Lymphocyte Antigens, Neoplasm Cancer Vaccines Toll-Like Receptors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Klebanoff Christopher A
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA.
Acquavella Nicolas
Yu Zhiya
Restifo Nicholas P
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Article Info
Journal
Immunological reviews
Abbr.
Immunol Rev
ISSN
1600-065X
DOI
10.1111/j.1600-065X.2010.00979.x
Published
2011-01-00
Pages
27-44
Language
English
Region
England
NLM ID
7702118
PMCID
PMC3075547
Subset
IM
Grants
Intramural NIH HHS · Z99 CA999999 · United States
Intramural NIH HHS · ZIA BC010763-05 · United States
Intramural NIH HHS · ZIA BC011037-03 · United States
External Links
PubMed source DOI: 10.1111/j.1600-065X.2010.00979.x PMC Full Text View journal details
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