For every advance in our understanding of the immunology of cancer, there is an increased appreciation of the complexity and tenacity of this family of diseases. Theory leads to treatments that show promise in vitro or in vivo, but often disappoint in clinical usage. The shortfall is often explained by the intimate interactions between cancer and the immune system, which in turn leads to new theory.
This pull-me, push-you progress seems inevitably headed toward an approach that combines universal mechanisms of biology with highly personalized treatment to reverse the steps by which cancer developed and grew in the patient, then effectively manage the patient against recurrence, and so cure cancer one patient at a time.
The clinical application of immune therapy exemplifies these issues. Physical removal of the TNF inhibitors from the blood reverses the universal mechanism by which cancer suppresses the immune response, thus allowing the patient’s immune system to destroy cancer cells as it should, and then restore normal immunologic homeostasis. This process is advanced by personalized support of the patient’s immune system, effectively arming the patient, and keeping him strong and healthy, while disarming the disease.
The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, though less favorably. Too often these therapies do not remove all cancer cells from the body, they do not address the immunosuppressive nature of the disease, but they can impair the patient’s immune response and may even weaken his resistance to the cancer.
The lack of personalization overall contributes to the problem that some patients benefit while others do not. Applying set treatment regimens to a heterodisperse group of patients because they have the same kind of cancer carries the risk of harming as many patients as one helps. This is especially a problem with chemotherapy when we apply a standardized dose and schedule of drug against a particular tumor type but don’t take into account the pathophysiology of the patient. Generally only 20-30% of patients show a significant tumor regression and clinical improvement using best-practices chemotherapy. The 70-80% who do not benefit cannot reliably be identified in advance based solely on tumor histology. The generally palliative benefit in the minority is difficult to measure against the acceleration of deterioration in the majority. Clearly a better method of applying particular systemic therapies is needed.
Immunepheresis has been described by some as the most promising method of killing cancer cells available today, both in terms of its rate of tumor necrosis and its low incidence of side effects and complications, and so is poised to play a greater role in cancer treatment in the future. But long-term questions remain and should be addressed even as the therapy is refined and more widely adopted. What prevents cancer recurrence – especially if cancer cells remain? If the factors that gave rise to the patient’s cancer in the first place are not changed, why would it not arise again? And for those patients in whom Immunepheresis is ineffective, could adjunct therapies improve outcomes? Immunepheresis is already for some patients a preferable therapy to surgery, chemotherapy and radiation, but with answers to those questions its full potential will be realized.
The Foundation believes that the “surveillance theory” of the immune system (Burnet, Thomas) might just be the key to answering these questions. According to this theory, the immune system is constantly vigilant against the presence of foreign cells, including genetically mutated cells like cancer. Its basic weapons against such threats are the immune cells of the innate and adaptive immune responses. The first causes of cell mutation may be normal and unavoidable – exposure to sunlight, carcinogens and stress among them. The disease state occurs when these mutant cells elude the immune system and proliferate, eventually impairing normal organ system function and ultimately destroying life itself.
The tumor-specific inflammatory response elicited by Immunepheresis is a prime example of the innate response. It is capable of specifically attacking tumor cells and reversing the disease process. Some proponents of the surveillance theory posit that the adaptive response can be similarly elicited, creating a kind of vaccination against cancer recurrence, capable of defeating cancer’s defensive mechanisms. When this is accomplished, we will truly be able to say that we can cure cancer – not by finding one “magic bullet” for all cancer, but by healing each cancer patient of his or her disease.