The immune system works to protect the body against infection and inflammation. Surprisingly, it also protects us from the development of cancer. The immune system includes the glands of the lymphoid system and blood cells. Normally, it can chemically “spot” and destroy faulty cells in the body, stopping the cancerous cells to develop further. On the contrary, a cancer can develop when the immune system is not strong enough to kill the cancer cells. Cancer cells undergo modification to evade recognition by the immune system. White blood cells called T-Lymphocytes usually are responsible for detecting these cancer cells.
Sreerupa Patranobish recently interviewed Dr. Rahul Ravilla, a physician at NYOH (New York Oncology and Hematology) in Albany, New York, whose pioneering efforts on immuno-therapy have helped abate dangerous cancers like melanoma. Physicians like Dr. Ravilla are using ipilimumab in cancer treatment and revolutionizing cancer therapy. Melanoma is a very dangerous cancer with high mortality rate. Dr. Ravilla has identified factors that can help in risk stratification and prevention of neurologic side effects including stroke in cancer patients. Contributions of Dr. Ravilla are at the forefront of informing cancer patients and physicians on the important risk and side effects after treatment with these special class of biologic immunoadjuvants.
SP: Welcome Dr. Ravilla
RR: Thank you for having me.
SP: What is cancer immunotherapy?
RR: Cancer immunotherapy treatments are those that enhances the power of the immune system to fight cancer. It represents the most recent promising cancer treatment approach since the development of the first chemotherapies in the 1940s.
SP: May you please briefly elaborate on how immunotherapy was developed?
RR: Cancer cells undergo modification to evade recognition by the immune system. White blood cells called T-Lymphocytes are responsible for detecting and eliminating these cancer cells. These cancer cells can express molecules that inactivate T-Lymphocytes. During cancer the T-Lymphocytes are inactivated. Thus, T lymphocytes fail to kill the cancer cells. More than a century ago, Dr. William Coley at Memorial hospital, New York advocated injecting bacterial toxins as a treatment for Ewing’s Sarcoma, a bone cancer. He noticed that several cancer patients with ‘erysipelas’ a skin infection, caused by streptococcus bacteria, went into remission. Dr. Coley hypothesized that the streptococcal infection induced immunity against cancer leading to regression of lesions. He started injecting these bacterial toxins, called Coley’s toxins, as a treatment for cancer. Although Coley’s toxins were successful in some cases, due to inconsistencies in results and reporting the interest in this therapy waned over time and with the introduction of chemotherapy and radiotherapy. Renewed interest appeared with the use of BCG vaccine as a treatment for early stage bladder cancer. After several decades and with contributions from Nobel laureate Dr Ralph Steinman, the first immunotherapy drug against castration resistant prostate cancer was approved by FDA.
SP: What are the different types of Immunotherapy?
RR: Several types of immunotherapy are used to treat cancer. Checkpoint inhibitors are drugs that can help the immune system respond more intensely to a tumor. Adoptive cell transfer aims to improvise the natural ability of the T-cells to fight cancer. Monoclonal antibodies are directed against specific target proteins on the cancer cells. Vaccines may also be used to ramp the body’s defences against cancer. For example, BCG, which stands for Bacillus Calmette-Guérin, the most common vaccine against tuberculosis, is an immunotherapy that is used to treat bladder cancer.
SP: What type of cancers can be treated with immunotherapy?
RR: Melanoma, a type of skin cancer, can be treated with immunotherapy. Immune checkpoint inhibitors affect a kind of white blood cell called T cells, which are then turned on against cancer. Immune checkpoint inhibitors like CTLA-4 and PD-1 inhibitors are currently being used to treat a wide range of cancers including melanoma, non-small-cell lung cancer, kidney cancer, bladder cancer, head and neck cancers and Hodgkin’s lymphoma.
SP: How were specific therapies developed for melanoma?
RR: Work in Dr. James Allison and Dr. Tasuku Honjo labs identified key proteins on T-Lymphocytes, which when blocked by antibodies led to destruction of cancer cells including Melanoma. This led to advent of a revolutionizing form of anti-cancer therapy called check point inhibitor therapy. These proteins are called CTLA-4 (cytotoxic T lymphocyte associated antigen-4) and Programmed cell Death protein 1 (PD-1). The antibody against CTLA-4 is called ipilimumab. It is now being used for treatment of melanoma and several other cancers.
SP: Who are eligible for immunotherapy?
RR: Individuals with cancers that are advanced (metastatic, or stage 4), cancers that have returned and spread after initial treatment or were diagnosed in an advanced stage.
SP: How long does the effects of immunotherapy last?
RR: Cancer immunotherapy offers the possibility for long-term control of cancer. Immunotherapy can train the immune system to remember cancer cells. Clinical studies on long-term overall survival have shown that the beneficial responses to cancer immunotherapy treatment are durable and there have been durability of remission.
SP: Does immunotherapy have any side effect(s)?
RR: Immunotherapy may not cause the same side effects as chemotherapy and radiation therapy. Cancer immunotherapy is focused on the immune system. Both chemotherapy and radiation damage healthy cells, commonly leading to hair loss and nausea/vomiting, side effects that may be less likely with immunotherapy. They are usually related to stimulation of the immune system and can range from minor symptoms of flu to major conditions like autoimmune disorders. These side effects are unpredictable, that is why we need to keep an eye out. I have identified that ipilimumab, the antibody used to treat melanoma, can significantly damage the spinal cord and may also cause lymphadenopathy (lymph node swelling, which may be a harbinger for additional cancer).
SP: What are the challenges of immunotherapy?
RR: Immunotherapy can work well for some cancers especially with advanced melanoma, who have had encouraging outcomes. The most challenging issue is that checkpoint immunotherapy doesn’t work for everyone – only a small number respond well to immunotherapy. The percentage is higher for some cancers such as melanoma. It may take some time to know the detailed mechanisms whether immunotherapy has worked because some people have a delayed response. This is a huge clinical challenge. Immunotherapy is not a new idea but is having more positive results. It though does offer new hopes for our patients.