Principles of biological therapy

This term encompasses a wide range of treatments, most of which are thought to act by indirect anticancer mechanisms rather than by a direct cytotoxic effect. The group includes a range of protein molecules from small peptide chemokines, larger cytokines, to complex antibody molecules made available by genetically engineering the production of large quantities by microbial and eukaryotic cell cultures. There is great potential for the continuing expansion of this field.

Interferons

Interferons are naturally occurring cytokines that mediate the cellular immune response. They have many actions in treatment of malignant disease with both antiproliferative activity, and stimulation of humoral and cell-mediated immune responses to the tumour that can result in an antitumour effect if the host effector mechanisms are present and fully competent.

Treatment with IFN has side-effects due to its foreign protein nature, most commonly flu-like symptoms which tend to diminish with time, and fatigue which generally does not and can be treatment limiting. In addition the drug has to be given as a subcutaneous injection over long periods of time, although conjugation with polyethylene glycol (PEG interferon) has led to a reduction in frequency of injection and severity of side-effects.

Interleukins

Originally described for their activity in modulating leucocyte activation, these cytokines have widespread activity in coordinating cellular activity in many organs. Current therapeutic interest has been mainly concentrated on interleukin-2, a recombinant protein used to activate T cell responses, often in conjunction with interferon-stimulated B cell activation. Antitumour activity has been observed in renal cell cancer and melanoma with responses in 10-20% of patients, occasionally for prolonged periods. Toxicity is common; acutely this includes the capillary leak syndrome with hypotension, whilst pulmonary oedema, autoimmune thyroiditis and vitiligo occur later.

Monoclonal antibodies

Monoclonal antibodies directed against tumour cell surface antigens are used in patients when they are 'humanized' by being genetically engineered as a chimera comprising a human constant region with the murine heavy and light chains of the antigen-combining site to reduce formation of blocking human anti-mouse antibodies

Immunotherapy

Cancer Tip Prostate Specific Antigen (PSA) has been called the most important tumor marker in oncology. Certainly in prostate cancer, it has revolutionized our ability to detect the disease early, as well as follow the course of the disease in patients after being treated with different therapies.

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