Cancer Immunotherapy and Preclinical Studies: Why We Are Not Wasting Our Time with Animal Experiments
Section snippets
Truly Tumor-Specific Antigens
One of the most important discoveries in tumor immunology following Gorer's [1] work was the identification of unique tumor-specific antigens [3], [4], [5], [6]. For example, a landmark paper by Klein and colleagues [7] demonstrated that a host could be immunized to reject its own cancer cells. The elegant experimental design of this study proved that autologous T-cell responses destroy autologous cancer cells; the study excluded the possibility that the antigens were artificially caused by
Proper choice of animal model
Almost all human tumors are established by the time they are recognized clinically. Therefore the main objective of the experimental immunologist is to select models that are relevant and have predictive value for patients who have established solid tumors, superficially spreading early-stage cancer or microdisseminated or dormant cancer cells. Furthermore, the experimental immunologist can address the problem of how to prevent some selected cancers. The main purpose of an animal model is to
Summary
Experiments using tumor transplantation have laid major foundations for immunology and cancer immunotherapy. Much evidence indicates that unique truly tumor-specific antigens are the most effective tumor-rejection antigens, and these antigens clearly occur on human tumors. Autologous tumor cell vaccination or autologous T-cell transfer allows T-cell responses to these antigens and opens the way to individualized cancer immunotherapy. Other promising targets are growth factors, growth factor
Acknowledgments
The authors thank Dr. Thomas N. Krausz for helping with the examination of the histologic specimens.
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2015, Current Opinion in ImmunologyCitation Excerpt :The term ‘established’ should be clearly defined, because it is frequently used for a cancer cell inoculum few days after injection (e.g. [73–75]). In our opinion, an ‘established’ tumor should have reached a clinically relevant diameter of 1 cm and lack the acute inflammatory reaction which is usually the case ∼14 days after the inoculation [76,77]. Such tumors are much more difficult to treat than early inflammatory lesions in mice, but come closer to the clinical situation.
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This work was supported by National Institutes of Health grants RO1-CA22677, RO1-CA37516, PO1-CA97296 and by the University of Chicago Cancer Research Center CA-14599.