7.0 THE ADVANTAGES OF CANCER IMMUNOTHERAPY

We hope the reader would have noticed from the preceding discussions in chapters 4—6 that the most salient point of immunotherapy as an anticancer agent is its exquisite specificity. The reliance of this technique on naturally occurring biological molecules to augment the immune system means that of all the scientifically validated methods for treating cancer, immunotherapy seems to be the most natural and friendly to the patient: therein lies the uniqueness and promise of cancer immunotherapy. It is well established that early detection of cancer is extremely important in the management and successful treatment of the disease. By taking advantage of the tremendous recognition capacity of the immune system, immunotherapists hope to develop much more sensitive and effective cancer diagnostic tools.
Due to the vital role that the immune system plays in the body’s defense, the kind of basic and applied research that CRI supports has many spin-offs that benefit other diseases. For instance, upon initial infection by HIV, it is common for the immune system to mount an attack on the virus resulting in the generation of HIV-specific CD8 killer T cells to destroy some of the viral invaders. As the disease progresses, it has been observed that CD4 helper T-cell populations begin to decrease and there is a direct correlation between the symptoms of an infected individual getting worse and the decline in CD4 helper T cells. It has been shown that the individuals who get infected with HIV but remain symptom-free for a long time have large and healthy populations of HIV-specific CD4 helper T cells that can produce enough IL-2 to keep the HIV-specific CD8 killer T cells growing and multiplying to fight off the deadly onward march of HIV. AIDS patients and others with compromised immune systems tend to develop a form of cancer called Kaposi’s sarcoma. It is believed but not proven that Kaposi’s sarcoma is caused by a Kaposi Sarcoma Herpesvirus (KSHV) infection. For sometime now, attempts by researchers to study how KSHV induces cancers in humans have been hampered because KSHV is unable to grow and divide outside the human body. Scientists are turning to immunotherapeutic approaches to circumvent these research obstacles.

In one study, scientists isolated CD8 killer T cells from people experiencing chronic infections with cytomegalovirus (CMV) and Epstein Barr virus (EBV). Comparative analyses of these cells with those from healthy individuals showed that CD8 killer T cells from the virus-infected individuals lacked a key co-stimulatory molecule called CD28. The scientists discovered that the loss of CD28 correlated with the lack of IL-2 in these individuals. However, when the researchers introduced the gene for CD28 via a gene courier (called a vector) into the CD8 killer T cells of these individuals, they were able to produce IL-2 independent of CD4 helper T cells, multiply and fight off the viral infections. One of the reasons why incurable viral infections like HIV, CMV and EBV become chronic is because our immune system cannot produce enough IL-2 to keep CD8 killer and memory T cells in a state of growth and proliferation. By the use of genetic engineering techniques to enhance the efficacy of adoptive T-cell immunotherapy, scientists have developed a vital tool that can be deployed against cancers and other cancer-causing viral infections like human papillomavirus, which causes genital warts and cervical cancer. These exciting results are very encouraging and they provide a compelling example of how active research in cancer immunotherapy has the potential to generate cures for other immune-related diseases.

7.1 The future of cancer immunotherapy
The future of cancer immunotherapy continues to be a promising one with an increasing number of new discoveries and techniques. Although our understanding of the human immune system is at a very advanced stage compared to the state of immunology during Coley’s lifetime, we are yet to obtain a complete understanding of this complex system. The reason why cancer immunotherapy is not yet in widespread use is that we do not know all there is to know about the human immune system. Despite this limitation, a lot of progress has been made in the field since the advent of Dr. Coley’s vaccine. For instance, adoptive T-cell transfer and vaccination is proving effective in the treatment of metastic melanoma: a disease that tends to cause death within six months of initial diagnosis. Intensive research in the last decade has provided vital new therapies for diseases such as bladder cancer, renal cell carcinoma, colon cancer, and some leukemias. Not surprisingly, these great strides in cancer immunotherapy have coincided with improvements in techniques such as genetic engineering and monoclonal antibody generation (discussed in chapter 8) and further discoveries in immunology.

In the future, cancer immunotherapies are expected to become a treatment option for cancer alongside the traditional methods such as surgery, radiation and chemotherapy. Used in combination with these three traditional methods, immunotherapies may increase the likelihood of long-term remissions for cancer patients. For example, the administration of immunotherapies to patients who are at a high risk of recurrence after surgery and other treatments may stimulate the immune system to destroy cancer cells left behind (micro metastases) and responsible for future recurrences. Studies are already underway that examine the use of immunotherapy in conjunction with radiation and chemotherapy to increase the effectiveness of patient responses. Now, let us take a brief look at two techniques that have ushered cancer immunotherapy into a new dawn that is full of promise.

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