Immunotherapy of cancer
- I McKenzie1
© BioMed Central 2003
Published: 1 October 2003
The use of appropriate mouse models in tumor immunotherapy is a crucial part of preclinical studies; indeed, without convincing 'mouse data', clinical studies usually do not ensue. However, there are problems in extrapolating from the mouse to the human; these will be separately considered for antibody-mediated and cell-mediated immunotherapy.
Monoclonal antibodies can be passively given to Scid mice bearing human tumors; the monoclonal antibodies may require complement and Fc receptors to mediate their effect, or act by inhibiting or stimulating signaling, leading to apoptosis. If complement is crucial, the mouse is not always the best model and additional complement may need to be provided. In preclinical studies in cancer, active immunization to produce only antibodies is not often done; although we have an example where such antibodies were ineffective in murine tumor models, but are apparently effective in humans.
In contrast to passive antibody administration, most efforts to examine cellular immunity involve direct immunization of mice, which examines: the antigen; the mode of delivery; and the immunogenicity of the antigen, including presentation by both class I and class II MHC molecules. Human antigens are 'foreign' to mice and the mouse H2 usually presents different peptides than does HLA. To overcome these problems, transgenic mice and tumors can be used if available–transgenic for tumor antigens and the MHC. If these are not available, mouse studies of an antigen are only a guide to immunogenicity. Adoptive transfer of human cells (either immune or non-immune T cells, dendritic cells, etc.) can be used to reconstitute mice, but this has inherent difficulties, as the infusion is a xenograft. In spite of all of the problems, useful preclinical data has emerged, and several examples of different modalities will be presented.