Targeting tumours by adoptive transfer of immune cells.
1. Surgery, radiotherapy and chemotherapy are the most widely used and well-established modalities for treating malignant diseases. Surgery is used to excise solid tumours and radiotherapy/chemotherapy are used for the treatment of liquid tumours and for solid tumours where there is a risk of micrometastases. A major drawback for both radiotherapy and chemotherapy is their lack of specificity for tumour cells. Both these treatments can destroy normal bone marrow cells and result in severe side-effects. 2. The impairment of haemapoiesis due to bone marrow destruction combined with the use of toxins in chemotherapy that inhibit the proliferation of immune cells leaves many patients immunocompromised. This complicates the development of prophylactic (vaccine) strategies for tumours where patients are undergoing conventional therapy. 3. An alternative approach is to expand and activate tumour-specific immune cells in vitro that can then be adoptively transferred back in large numbers. This is defined as adoptive immunotherapy and has the advantage of potentially bypassing the immuno-inhibitory effects of conventional therapies. 4. Transferred immune cells have been shown to mediate tumour regression in patients by both direct and indirect mechanisms. The immune cells used include tumour reactive T lymphocytes and dendritic cells, which elicit tumour specific responses. 5. Many novel cell-based immunotherapeutic strategies developed in murine tumour models are now being applied in human clinical trials. The malignancies targeted include melanoma, chronic myelogenous leukaemia and breast, ovarian, colon and kidney cancers. In the present review, we discuss these novel cell-based strategies and the implications they have for the future treatment of human malignancies.
Macary
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Immunology Program and Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Too
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Dai
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D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D016131:Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000637:transplantation*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*