Cancer Immunotherapy
The concept of immunity to infectious diseases has existed since 1796 when Edward Jenner vaccinated a young boy against smallpox by inoculating him with cowpox. This was not the first case of vaccination but it is one of the best known. The more vague idea of a possible immunity to cancer has existed since the 19th century. For example in 1884, Russian playwright and less known Physician Anton Chekhov noted that erysipelas infection in cancer patients sometimes resulted in tumour regression (1).
In the early 20th century, Paul Ehrlich conceived the idea of ‘Immune Surveillance’. He suggested that the immune system suppressed the development of tumours much like the spreading of infections, once they were detected (2).
There was little advancement in the field until the 1950s when Edward J. Foley began experimenting with tumour transplantation in mice. He found that on repeated transplantation and removal of tumours, the mice developed a greater resistance to each subsequent tumour (3). This led to the concept of tumour specific antigens. At the end of this decade, Interferon, a “virus fighting protein” was discovered and would later be found to fight tumours (4). Furthermore, the New York Cancer Research Institute became exclusively dedicated to researching immunotherapy.
During this time, a growing school of thought believed that viruses caused cancer. In the 1960s, more evidence emerged detailing the role of the immune system in suppressing cancer and in 1963, Garry Abelev discovered the first cancer specific antigen; alpha fetoprotein (AFP) (5).
However, in 1974, tumour immunosurveillance was discredited by a study’s results that have yet to be entirely resolved. Osias Stutman reported that athymic (nude) mice are no more susceptible to the development of chemically induced tumours in incidence or onset. This finding was inconsistent with the idea that the immune system suppressed or eliminated tumours in early oncogenesis (6).
Despite this setback, in the 1980s great advancement was made in understanding and utilising the immune response to tumours. In 1983 Catherine Uyttenhove and Thierry Boon showed that tumours escape the immune system of mice by antigen-loss variants (7). This helped to partly resolve the results of the Stutman paper and develop the dynamic concept of the “three phases of immunoediting” (elimination, equilibrium and escape).
During this time monoclonal antibodies were developed to battle various diseases including B cell lymphomas. Immunotherapy has since employed many methods to treat cancer including; targeting antigen specific tumours with vaccines, modulating regulatory T cell responses and immune chackpoint blockade.
References
1. A. Chekhov, M.D., and Coley's Toxins. New England Journal of Medicine. 1987;317(7):457-457.
2. Nature.com. Milestone 3 : Nature Milestones in Cancer [Internet]. 2015 [cited 26 November 2015]. Available from: http://www.nature.com/milestones/milecancer/full/milecancer03.html
3. Foley, E. J. 1953. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Research. 13: 835.
4. Isaacs A, Lindenmann J. Virus Interference. I. The Interferon. Proceedings of the Royal Society B: Biological Sciences. 1957;147(927):258-267.
5. Abelev G, Perova S, Khramkova N, Postnikova Z, Irlin I. PRODUCTION OF EMBRYONAL α-GLOBULIN BY TRANSPLANTABLE MOUSE HEPATOMAS. Transplantation. 1963;1(2):174-180.
6. Schreiber T, Podack E. A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas. Br J Cancer. 2009;101(3):381-386.
7. Uyttenhove C. Escape of mouse mastocytoma P815 after nearly complete rejection is due to antigen-loss variants rather than immunosuppression. Journal of Experimental Medicine. 1983;157(3):1040-1052.