Immunotherapy in mice of virally induced tumors using syngeneic monoclonal antibodies

This thesis deals with one variant of immunotherapy, namely the use of tumor-specific antibodies to induce tumor destruction. The experimental work falls apart into four succeeding phases: a) definition of the model, which means the choice of the animal and the tumor, the generation and characterization of the monoclonal antibodies; b) testing the monoclonal antibodies for their ability to find the right target io_YiYOi c) testing these antibodies on the suitability for immunotherapeutical purposes; d) investigations on the underlying mechanism which may lead to tumor cell destruction. An artificial tumor metastasis model was chosen to imitate in a controlled way metastatic cancer, which is still the major problem in conventional therapy of malignant neoplasias. The non-producing Rauscher virus induced myeloid leukemic cell line RMB-1 was selected (De Both et al., 1981). Experiments carried out in Chapters II - VI. the order as outlined above are reported in the Chapter II deals with the characterization of two monoclonal antibodies directed against the viral protein p12, its precursors and a glycosylated polyprotein. In Chapter III results on specific io_yiyg targeting of both monoclonal antibodies are reported and discussed. Chapter IV deals with the use of one monoclonal antibody for immunotherapy in a disseminated tumor model; its possibilities and limits are investigated. In Chapter V an attempt is made to explore the underlying mechanism by carrying out io vivo and io vitro experiments and by histological studies. Chapter VI is directed to one aspect of the underlying mechanism, namely delayed-type hypersensitivity elicited by the tumor cells in the immunocompetent host. In Chapter VII the model is discussed in the context of the contemporary literature