Biological modifiers and their role in cancer therapy.

Biological modification in cancer therapy involves many different strategies and substances. Bacterial products with established usefulness include BCG, C. parvum and L-Asparaginase. Immunotherapy with such agents has not, however, found general application, although revived interest in 'Coley's mixed toxins' (used earlier this century) paralleled the development of their presumed effector molecules, tumour necrosis factor and lymphotoxin. Many other Cytokines, both natural or recombinant, are now produced on a vast scale following the recent biotechnology revolution. Of these, Alpha Interferons have already proved useful in hairy cell leukaemia, carcinoid tumours, renal cell cancer, Kaposi's sarcoma, chronic granulocytic leukaemia and certain lymphomas, whilst their use as adjuvants or in combination is currently being investigated. More recently, Interleukin-2, which stimulates the clonal expansion of activated T-cells, has shown promise both as a single agent, and when used with lymphokine activated killer (LAK) cells or tumour infiltrating lymphocytes (TILS). A different approach involves the Colony Stimulating Factors such as G-CSF and GM-CSF which reduce the degree and duration of treatment-related myelosuppression, thereby allowing more intensive cytotoxic or radiation therapy, as well as facilitating early recovery following bone marrow transplantation. Monoclonal antibodies have not proved as specific for malignant cells as was originally hoped, but certain tumours, such as lymphoma, are now realistic targets for therapy. Increasingly sophisticated effector mechanisms (e.g. conjugated pro-drugs) and genetically engineered "humanised" monoclonal antibody hybrids present the brightest hopes for the future. Biotherapy, the "fourth modality of cancer treatment" has already assumed its place alongside surgery, radiotherapy and cytotoxic chemotherapy, and will grow in importance as our understanding of the molecular biology of cancer increases in the coming decades.