My career began in the 1970s in the field of cancer immunology, a subject, which nowadays is at the forefront of cancer research, holding the promise of delivering new therapies for treating patients suffering from a wide range of cancers. Many scientists working in the field are not readily aware that the very first research papers documenting immunity against cancer were published in 1955 in the British Journal of Cancer by Robert (Bob) Baldwin, working in Nottingham, England. Fifty years on from his pioneering work, we have a greater understanding of how the body’s immune system acts as a surveillance mechanism to constantly patrol the body and destroy newly formed tumor cells, and the conditions where tumors escape immune detection and their progress is unchecked. In the 1960s and 1970s there was an explosion in research aimed at stimulating host immunity, without the in-depth knowledge we now have on the genetic basis of cancer and malignant progression and spread of the cancer beyond the confines of the primary tumor.
Robert Baldwin pioneered research into immune-stimulants, using for example bacteria, such as the attenuated BCG organism used to immunize against tuberculosis, and led the field in the production and clinical application of monoclonal antibodies; this has resulted in several antibody based therapies being introduced into the clinic. For example, Herceptin, an antibody that recognizes a protein known as Her2/neu, is used to treat a sub-group of breast cancer patients. Because other tumors express this protein, vaccine therapy against Her2/neu in prostate as well as breast cancer is undergoing trials at the present time. I was fortunate enough to work at the Nottingham Cancer Research Campaign Laboratories in the 1970s, where this experience acted as a springboard for my continuing interest and career in immunology, principally cancer immunology.
Having subsequently worked at Sheffield Medical School, and The National Cancer Institute in Bethesda and in Philadelphia, in 1996, I found myself back in Nottingham, heading my own team of scientists, now established as The John van Geest Cancer Research Centre, where our research interests are clearly focused on (1) identifying new cancer genes and antigens for developing personalized medical care through the use of cancer biomarkers, and (2) developing new forms of immunotherapy, where the combination of therapeutic vaccination and treatments designed to decrease the effectiveness of tumor escape from immune detection, are truly “center stage.” The work at our Institute and other institutes, will, I believe, make a real impact on patient survival and clinical management in the next decade. All of the major Pharmaceutical companies have entered the race to develop immunotherapy products and a variety of approaches are now undergoing clinical trials or are already approved for use by the FDA.
What makes us believe in the immune system as a means of treating cancer is the fact that in cases where the immunity is compromised, either through the use of immune-suppressive drugs or by infection with, for example, HIV, then cancers arise. We now have an in-depth understanding of how cancer occurs and progresses, the immune cells that mediate anti-cancer activity and the molecules that switch immunity off causing a “depression” in immune function. The controversial research into “cancer stem cells” now requires considerable resource and research input over the next decade or so. It will be important to define their role in tumor progression and determine their susceptibility to immunotherapy. Their mere existence in many cancers has been difficult to establish since they represent a minority population within tumors, although where they have been identified it is true to say that they appear to represent a highly aggressive, therapy resistant cell type with the ability to self-renew and give rise to differentiated cells within the tumor mass. This finding, together with our increasing understanding of “Tumor cell plasticity” will be important to consider as we aim to utilise the power of the immune system to successfully treat cancer.