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16 Cancer Immunotherapy

Drew Pardoll, Gary J. Nabel


Although gene therapy was originally conceptualized as a treatment for heritable genetic diseases via replacement of defective genes, it has come to encompass the much broader goal of utilization of gene transfer to alter biological systems with therapeutic intent. This expanded vision of gene therapy is most dramatically exemplified by the tremendous number of genetic approaches to manipulate the immune system. Genetic manipulation of antitumor immunity has been the major arena with 58 of the first 100 approved protocols in cancer gene therapy targeting the immune system. Genes encoding immune regulatory molecules and tumor antigens have been introduced into tumor cells, as well as various viruses and bacteria, to create cancer vaccines. More recently, in vivo gene-transfer strategies have demonstrated the capacity to turn on or off specific immune responses. Thus, although activation of antitumor immunity has been the focus of the majority of initial approaches, it is now clear that analogous gene-transfer approaches can be effectively utilized to inhibit or suppress certain immune responses as treatment for autoimmune disease or transplant rejection. Through the combination of improved vectorology and the greater understanding of molecular pathobiology, a large proportion of major diseases may thus become amenable to some form of gene therapy.

History of Genetically Altered Whole-cell Tumor Vaccines
Whole-cell tumor vaccines mixed with adjuvants have been tested extensively in multiple cancer types for decades with multiple reports of either anecdotal responses or improved outcome relative to historical controls. These vaccines have consisted of either...

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