Manipulation of host resistance in cancer therapy
The notion that malignant cells may be subject to control by the immunological network of the host has developed basically from studies of the immune rejection of rodent tumours, particulary those induced with chemical carcinogens or oncogenic viruses [15, 25, 98]. In one series of studies reported some 25 to 30 years ago, it was established that sarcomas induced by polycyclic hydrocarbon carcinogens in rodents of inbred (syngeneic) strains grew progressively following transplantation into compatible recipients [3, 36, 80]. However, pre-immunization of normal animals with tumour cells treated so as to restrict their progressive growth led to the development of a specific tumour immunity, so that a subsequent challenge with cells of the immunizing tumour was rejected. The repertoire of tumours in which there is conclusive evidence for the expression of antigens which can be manipulated to produce tumour rejection responses was rapidly expanded following these early studies. It now includes tumours of many types including carcinomas and sarcomas induced with a broad spectrum of chemical carcinogens [15], many of these belonging to the classes (polycyclic hydrocarbons, nitrosamines, amino azo dyes, and aromatic amines) which are known, or suspected to be, human carcinogens. Rodent tumours induced with DNAand RNA-containing oncogenic viruses have also been shown to express antigens able to induce turnout rejection [41, 50]. Recently tumours induced with UV-radiation also were shown to express antigens which elicit tumour rejection [57]. Faced with this wealth of evidence from rodent tumour studies that the adaptive immune system of the host can respond to tumours, it is not surprising that consideration has been given over the past 10 years or more to the possibility that specific immunotherapy may be introduced for cancer treatment. This approach initially received encouragement from early studies reporting that administration of vaccines containing radiation attenuated leukaemia cells with BCG as an immunostimulant produced a therapeutic response in acute lymphoblastic leukaemia [60]. Also in vitro cytotoxicity tests with blood lymphocytes from cancer patients