Hybrid Cell Vaccination for Cancer Immunotherapy
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HYBRID CELL VACCINATION FOR CANCER IMMUNOTHERAPY Peter Walden Department of Dermatology
Medical Faculty Charité Humboldt University Berlin, Germany
1. INTRODUCTION 1.1. Tumour Immunology The immune surveillance hypothesis proposed by Macfarlane Burnet in 1970
(Burnet, 1970) summarised nearly a hundred years of research on the role of the immune system in cancer. This research had cumulated a substantial body of evidence for the major contribution of the immune system to the control and eradication of cancer. Pathological studies suggested a much more frequent incidence of initial tumour devel-
opment than what becomes clinically manifest. Burnet’s studies had indicated that at a
thymus dependent, hence, T cell mediated mechanisms control tumour, may stop its growth and prevent cancer. Since then, tumour associated antigens for T cells were identified, tumour specific antibodies and T cell were isolated from peripheral blood and tumour of cancer patients, and T cell growth and differentiation factors were successfully employed for the treatment of cancer. Tumour infiltrating T lymphocytes were shown to exhibit at least in parts tumour specificity. All these observations confirmed the central role of the immune system and especially of T lymphocytes in tumour biology, and prove that the immune system has the capacity to identify and destroy tumour cells.
Notwithstanding these evidences for the high efficiency of the immune surveillance system, cancer exists among the major health problems of mankind. The failure of the immune system in cases of cancer is the hub of tumour immunology, and a focus of all endeavours towards new strategies for the treatment of cancer. The cause of this failure or, in immunological terms, the reason for the insufficient immunogenicity of the tumour may be in the tumour cells themselves. A lack of antigenicity or a loss of antigens under immune selection pressure renders tumours invisible to the immune system. There may be defects in the immune system such as antigen presentation defects or a lack of suitable tumour specific T cells in the patient’s T cell receptor repertoire because of a Cancer Gene Therapy: Past Achievements and Future Challenges, edited by Habib Kluwer Academic/Plenum Publishers, New York, 2000.
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non-permissive immune genetics or because of immune tolerance. The interaction of tumour and immune systems may result in immune suppression or clonal exhaustion, i.e. a deletion of the tumour specific T cell clones induced by their anti tumour reactions. Finally, there may be deficits in the immune regulatory support for the development of tumour specific cytotoxic T lymphocytes that prevents their induction. Spontaneous tumour regression has been reported for different cancers, and central regression zones in melanoma lesions with simultaneous tumour progression in the border zones can be very frequent. These observations strongly suggest that the relationship of tumour and immune system in cancer is a dynamic relationship with an ongoing struggle
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