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Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells
Author(s) -
Spaner David E.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0104016
Subject(s) - biology , immune system , cancer research , cancer , carcinogenesis , immunology , stat protein , cancer cell , effector , signal transduction , microbiology and biotechnology , stat3 , genetics
Immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor‐β, prostaglandin E 2 , interleukin (IL)‐10, and IL‐6, are made frequently by cancer cells. These factors, along with others, can inhibit the development and function of tumor‐reactive effector T cells and the clinical results of cancer vaccines. Production of these factors by tumor cells is associated with disease progression and may represent an active immune surveillance escape mechanism. However, a number of factors appear to be made directly in response to signaling molecules, such as RAS, AKT, and signal transducer and activator of transcription 3, which are activated as a result of genetic events that occur during oncogenesis. Methods to overcome the negative effects of immunosuppressive factors, which are “hard wired” into gene programs of cancer cells, might then improve the results of cancer vaccines. For example, specific blocking antibodies, which recognize such factors, or kinase inhibitors, which block the signaling pathways that lead to their production, could potentially be used as vaccine adjuvants. The effects of immunosuppressive factors may also be “turned off” by cytokines with tumor suppressor properties. The enhanced clinical and immunological effects of melanoma vaccines observed after the administration of high doses of interferon‐α2b provide a “proof of principle” in human patients, that agents which counter the gene programs of cancer cells, causing them to intrinsically resist tumor‐reactive T cells, may improve significantly the efficacy of cancer vaccines.