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Over the past ten years significant advances have been made in
the fields of gene therapy and tumour immunology, such that there
now exists a considerable body of evidence validating the proof
in the principle of gene therapy based cancer vaccines. While
clinical benefit has so far been marginal, data from preclinical
and early clinical trials of gene therapy combined with standard
therapies are strongly suggestive of additional benefit. Many
reasons have been proposed to explain the paucity of clinical
responses to single agent vaccination strategies including the
poor antigenicity of tumour cells and the development of
tolerance through down-regulation of MHC, costimulatory, signal
transduction, and other molecules essential for the generation of
strong immune responses. In addition, there is now evidence from
animal models that the growing tumour may actively inhibit the
host immune response. Removal of the primary tumour prior to T
cell transfer from the spleen of cancer bearing animals, led to
effective tumour cell line specific immunity in the recipient
mouse suggesting that there is an ongoing tumour-host
interaction. This model also illustrates the potential
difficulties of clinical vaccine trials in patients with advanced
stage disease
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