Detection of cellular immunity to tumor antigens of a guinea pig hepatoma by inhibition of macrophage migration.
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Biomedical subjects
Publications and source records attributed to B Zbar.
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Supernatant fluids of specifically stimulated lymphocyte cultures were purified. Fractions containing migration inhibition factor when injected intra-dermally into strain-2 guinea pigs produced a reaction similar in appearance to delayed cutaneous hypersensitivity. There was an accumulation of mononuclear cells at the injection sites and the growth of syngeneic tumor grafts at the sites was suppressed.
Injection of living Mycobacterium bovis (strain BCG) into established intradermal tumors caused tumor regression and prevented the development of metastases.
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The intradermal inoculation of mixtures containing living tumor cells and living Mycobacterium bovis (strain BCG) into unimmunized syngeneic guinea pigs results in an inflammatory reaction to the BCG, and there is no progressive tumor growth. In the absence of BCG the tumor grows progressively, metastasizes, and kills the animal. By conventional methods, it has not been possible to immunize syngeneic guinea pigs to the tumor used. Guinea pigs that receive mixtures of BCG and tumor cells, however, develop specific systemic tumor immunity as measured by delayed cutaneous hypersensitivity and by suppression of tumor growth.
Successful treatment of a solid tumor was accomplished by repeated intradermal injection of living tumor cells.
Tumor immunity to a transplantable diethylnitrosamine-induced hepatoma in inbred guinea pigs has been found to be immunologically specific and cell mediated. We have investigated this cellular immunity using a quantitative, reproducible, and simple assay based on the ability of leucocytes to inhibit the incorporation of tritiated thymidine (TdR(3)H) by tumor cells. Tumor cell suspensions were obtained from the ascites form or tissue culture monolayers of the hepatoma. Cells from the peritoneal exudate of immunized guinea pigs inhibited tritiated thymidine uptake by tumor target cells to a significantly greater degree than cells from the peritoneal exudate of unimmunized animals. Immune lymph node, peripheral blood, and spleen leucocytes were not inhibitory. The assay was sufficiently sensitive to detect relatively weak tumor immunity. The in vitro inhibition was correlated directly with the presence of delayed hypersensitivity and/or inhibition of tumor cell growth in local passive transfer studies. Irradiation of peritoneal exudate cells (3000 R) blocked their inhibitory effects on tumor cells. Fractionation of the peritoneal exudate cells by centrifugation in zones of bovine serum albumin of different density also revealed the lymphocytes to be responsible for the specific inhibitory effects whereas macrophages inhibited in an immunologically nonspecific fashion.