Antitumor vaccines, immunotherapy and the immunological constant of rejection.
Anticancer vaccines have not matched the clinical expectations projected from their ability to induce consistently systemic anticancer T-cell responses. Thus, a dichotomy is observed between the immunological and clinical endpoints of anticancer immunization. Anticancer vaccines have clearly demonstrated that highly specific T-cell responses can be induced that can recognize autologous cancer antigens in patients with cancer. This ability is an outstanding achievement of modern biotechnology, yielding one of the most specific types of potential anticancer reagents. However, systemic, vaccine-induced anticancer responses exemplify a broader immunological paradox: cytotoxic T-cells can coexist within the same organism with their target cells not only in the context of cancer, but also in the context of chronic infections, well-controlled allo-transplant reactions and autoimmunity. According to this view, anticancer immune responses are a facet of a tissue-specific autoimmune phenomenon specific for cancer tissue that may or may not result in the successful immune-destruction of target cells, depending on an assortment of genetic factors related to the background of the host or evolving phenotypes of a heterogeneous cancer environment. This feature article summarizes the current understanding of the mechanisms leading to tumor rejection in humans as well as in experimental models, in the context of the broader immunological phenomenon leading to tissue-specific destruction. Anticancer vaccines that may not induce clinically significant anticancer responses independently could function as a unique tool to enhance the specificity of the response of the host against cancer, provided that strategies are implemented to amplify the immune reaction initiated by vaccine-induced antibodies and/or T-cells.
Wang
Ena
E
National Institutes of Health, Department of Transfusion Medicine, Building 10, Room 1C711, Clinical Center, Bethesda, MD 20892, USA.
Monaco
Alessandro
A
Monsurró
Vladia
V
Sabatino
Marianna
M
Pos
Zoltan
Z
Uccellini
Lorenzo
L
Wang
Jeanne
J
Worschech
Andrea
A
Stroncek
David F
DF
Marincola
Francesco M
FM
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D019496:Cancer Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D019496:Cancer Vaccines