Animal models of tumor immunity, immunotherapy and cancer vaccines
Introduction
Animal models have played a critical role in establishing basic paradigms of tumor immunology because they provide an in vivo milieu that cannot be reproduced in vitro. As novel immunotherapies and cancer vaccines have been developed, animal models have also played an important role in pre-clinical testing for therapeutic efficacy. Historically, investigators have used transplantable tumor models, in which inbred animals are inoculated with tumor cells derived from the same genetic strain. The tumors were initially derived from spontaneously occurring malignancies or induced by chemicals or irradiation, and maintained either by in vivo or in vitro passage. As the tumor immunology field has moved towards developing cancer vaccines and other novel cancer immunotherapies, the same transplantable tumor models have been used to test therapeutic efficacy. Unfortunately, many of these tumor models are not good predictors for human clinical trials, as numerous therapies that look promising in experimental animals have turned out to be ineffective in patients. Although immunotherapy and cancer vaccine studies are moving away from using transplantable tumor models, they remain a mainstay for immunologists examining issues of basic tumor immunology. This review will briefly describe the pros and cons of transplantable tumor models and then focus on the recently developed transgenic mouse models in which tumors develop spontaneously. A brief overview of other mouse models that have been useful in defining basic principles of tumor immunology will also be discussed.
Section snippets
Transplantable tumor models
Although transplantable tumors have long been integral to tumor immunology research, they have several characteristics that limit their applicability to human disease and make them less than optimal for predicting immunotherapy efficacy in patients. First, most transplantable tumors were derived many years ago, and today’s ‘syngeneic’ mouse strains may no longer be fully syngeneic with these tumors. In addition, some transplantable tumors have picked up endogenous viruses and express viral
Models for testing immunotherapy and cancer vaccines
In developing better animal models for both immunotherapy and cancer vaccine studies, investigators have tried to address the problems associated with transplantable tumors and to develop experimental systems that more closely mimic human malignancy. Efforts have been directed towards developing transgenic mouse models in which tumors develop spontaneously and progress through the known pre-malignant and malignant stages; defined human tumor antigens are expressed so that the host is tolerized
Conclusions
Although most investigators believe that animal models can provide useful pre-clinical information about novel immunotherapies and cancer vaccines, others have argued that animal studies are uninformative because they are not predictive of results with humans. If poor prognostic results from animal studies are due to inadequate models, then better models must be developed. As tumor immunologists select the models they use, they should ensure that they mimic as closely as possible the human
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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of outstanding interest
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