Principles of cancer treatment by immunotherapy

Results from animal studies and human cancer patients indicate that a functional cancer immunosurveillance process exists in vivo, acting as an extrinsic tumour suppressor. Initiation of an anti-tumour immune response occurs when the immune system becomes alerted to the growing tumour. This may result in tumour elimination, or alternatively, due to the inherent genetic instability of tumours, to the selection of tumour variants that are resistant to immune attack. Hence, it is counterintuitive to reimmunize with autologous tumour. Ex vivo stimulation and expansion of T-cells in combination with lymphodepleting chemotherapy has been successful, resulting in dramatic tumour regressions, but is patient specific, expensive and time consuming. New and cleverer in vivo approaches to harness a new wave of immune attack must be taken, including enhancing tumour epitopes to increase their immunogenicity, and in vivo targeting of antigen-presenting cells that stimulate cellular immunity. Monoclonal antibodies have recently proved their clinical utility, with ritixumab being approved for treatment of non-Hodgkin's lymphoma and herceptin as adjuvant treatment and for advanced or recurrent breast cancer. These antibodies act alone by directly inducing apoptosis, blocking growth factors and/or stimulating antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity. The radiolabelled antibodies bexxar and zevalin have also been approved for treatment of non-Hodgkin's lymphoma.