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Abstract
Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2) and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.
Highlights
There is broad appeal for the concept of treating cancer with the immune system
The protective immunity induced by syngeneic tumor vaccines appears to be mediated most directly by T-cells, and in many studies, depletion of CD8+ T cells abrogates the protective effect of syngeneic tumor cell vaccines [12], suggesting cytotoxic Tcells are critical to that protective immunity
In the late 1980s, it was found that melanomas expressed shared antigens recognized by CD8+ cytotoxic T lymphocytes (CTL) [16]
Summary
Subsequent studies with adoptive transfer of tumor-infiltrating lymphocytes (TIL) expanded ex vivo in IL-2 were associated with clinical regressions in 55% of patients in early studies [38], but this has largely been abandoned due to failure to maintain response rates that were convincingly better than that expected from high dose IL-2 alone [39,40]. Summary Immune therapy of cancer may take many forms, specific or non-specific, adoptive or active, and may target antibody, T cell, and innate immune mechanisms Each of these approaches has proven or potential value, and the complexity of the host: tumor relationship is such that a narrow focus on a single immunotherapy strategy is likely to fail. We argue that the lesion in current approaches to cancer vaccine therapy is our poor understanding of the mechanisms that limit expansion, activation, and effector function of tumor-antigen specific T cells. Bypassing this process by use of adoptive therapy is a reasonable short-term effort, but to advance the field of tumor immunology and immunotherapy it will be critical to elucidate the immunobiology of the host-tumor relationship. Vaccines with defined antigens are ideal for investigations of this type
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