Document Detail


Re-purposing cancer therapeutics for breast cancer immunotherapy.
MedLine Citation:
PMID:  22454154     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
After decades of work to develop immune-based therapies for cancer, the first drugs designed specifically to engage the host anti-tumor immune response for therapeutic benefit were recently approved for clinical use. Sipuleucel-T, a vaccine for advanced prostate cancer, and ipilimumab, a monoclonal antibody that mitigates the negative impact of cytotoxic T lymphocyte antigen-4 signaling on tumor immunity, provide a modest clinical benefit in some patients. The arrival of these drugs in the clinic is a significant advance that we can capitalize on for even better clinical outcomes. The strategic and scientifically rational integration of vaccines and other direct immunomodulators with standard cancer therapeutics should lead to therapeutic synergy and high rates of tumor rejection. This review focuses on the use of cyclophosphamide, doxorubicin, and HER-2-specific monoclonal antibodies to dissect mechanisms of immune tolerance relevant to breast cancer patients and illustrates how appropriate preclinical models can powerfully inform clinical translation. The immune-modulating activity of targeted, pathway-specific, small molecule therapeutics is also discussed. Fully understanding how cancer drugs impact the immune system should lead to the ultimate personalized cancer medicine: effective combinatorial immunotherapy strategies that simultaneously target signaling pathways essential for tumor growth and progression, and systematically break multiple, distinct immune tolerance pathways to maximize tumor rejection and effect cure.
Authors:
Leisha A Emens
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review     Date:  2012-03-28
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  61     ISSN:  1432-0851     ISO Abbreviation:  Cancer Immunol. Immunother.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-10-01     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1299-305     Citation Subset:  IM    
Affiliation:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231-1000, USA. emensle@jhmi.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / immunology*,  therapy*
Congresses as Topic
Cyclophosphamide / therapeutic use
Doxorubicin / therapeutic use
Female
Humans
Immunotherapy / methods*
Receptor, erbB-2 / antagonists & inhibitors
Grant Support
ID/Acronym/Agency:
P50 CA088843/CA/NCI NIH HHS; P50CA88843/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 23214-92-8/Doxorubicin; 50-18-0/Cyclophosphamide; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections

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