Today more people die due to cancer than any other disease in the world. By the time you finish reading this article, more than 5 people would have died in India alone due to cancer. After decades of research and zillions of dollars spent to find a magic bullet, scientists and clinicians have finally come closer to tackle this debilitating disease in what they call as the fifth pillar of cancer therapy known as “Cancer Immunotherapy”. By far, cancer immunotherapy is considered "the most promising frontiers of cancer research of our times with complete remission and high survival rates". Some of the promising and clinically approved recent cancer immunotherapy approaches are discussed below.
Antibody-Based Cancer Immunotherapy
In this approach, antibodies specific to a cancer cell are generated and used to treat the disease. The first step in the process of antibody-based immunotherapy is to screen for and recognize specific cancer or tumor antigen (TA). These TAs are predominantly expressed by cancer cells as compared to normal cells. The screening of patient tissue is done to find any specific TA, against which the antibodies are then generated. Currently, for almost every TA there are commercially available antibodies. After matching the antigen-antibody, the patients are given different doses via various modes, which depend on the target organ. Once these antibodies are in the system they recognize the tumor cells and eliminate them via an antibody-dependent cell mediated cytotoxicity (ADCC) by activating the patient’s own immune system.
Does Antibody-Based Cancer Immunotherapy Work in all Patients?
The immunotherapy approach is a personalized therapy, where specific antibodies are used against patient-specific TAs. Thus, a single antibody approach may not work in all patients and the success depends upon the identification of the target cancer antigen. Before opting for any kind of immunotherapy, a patient has to go for rigorous screening and tests to check for the suitability and type of immunotherapy. Physical examination, blood tests, body scans, histological analysis, and antigen specificity should be done before opting for this therapy.
Advantages: This technique has limited non-specific targets and hence the patient does not suffer from side effects like fatigue, nausea, appetite changes, hair loss or skin cell damage. The remission rates are higher as compared to traditional approaches like chemotherapy or radiation therapy.
Limitations: In advanced cancer cases, the patient may also have to go for a shorter period of radiation or chemotherapy sessions along with antibody treatments.
Adoptive Cell Transfer Based Cancer Immunotherapy
In Adoptive Cell Transfer (ACT) patients’ own immune cells (known as T (thymocytes) cells or NK (Natural Killer) cells) are isolated from blood and expanded under laboratory conditions to increase their number. After expansion, these cells are further activated in presence of tumor antigens. Once activated in the laboratory, these cells are subsequently transferred back to the same patient where they eventually recognize the tumor cells and eradicate them while sparing the normal cells.
Advantages: ACT-based approach is better than cancer/radiation therapy as the side effects are minimal. Further, compared to only antibody-based approach ACT is more potent in eradicating cancer cells directly. In most of the cases, this technique can be used alone without alternate cancer therapy approaches like chemo or radiation therapy, but that depends on the tumor type and stage.
Limitations: ACT-based immunotherapy has a limitation in terms of durability, as most of these cells are eventually eliminated from the body and thus these cells have to be given at regular intervals like antibody-based therapy.
Chimeric Antigen Receptor Based Cancer Immunotherapy
Never generation cancer immunotherapy research has culminated in the development of Chimeric Antigen Receptor (CAR) based T cells or Natural Killer (NK) cells. In this technique, the patient’s immune cells are isolated from their blood as above (ACT) and expanded under laboratory conditions. Once an optimal cell number is reached they are further genetically engineered to express a specific antibody-based receptor (chimeric receptors), which is directed against the TA present on the patient’s cancer cells. The engineered immune cells (known as CAR cells) are then transferred back to the blood of the patient, where they recognize the affected cancer cells and eliminate them in the process.
Advantages: CAR cell-based immunotherapy is more specific, potent and long-lived. This technique has very limited side effects, which may be mild or rarely severe but manageable. Additionally, this is the most promising cancer immunotherapy approach which has met with unprecedented success.
Limitations: Currently very few places in the world offers this type of treatment. The cost of this technique is very high but expected to go down in the future.
Cancer Immunotherapy Centers in India
Cancer immunotherapy can be received either at the doctor’s clinic, hospital or at home, but should be delivered only by trained clinicians. Currently, there are few centers/hospitals in India which offer this type of treatment. Hospitals like Tata Memorial Hospital, Mumbai; Max Healthcare, Delhi; NanaVati Hospital, Mumbai; and Medanta, the Medicity, Gurgaon, Primus Super Speciality Hospital provide antibody-based cancer immunotherapy, but none of them have CAR-T based facility.
In the year 2017, Food and Drug Administration (FDA), USA have approved two CAR-T cell-based drugs; Tisagenlecleucel (Kymriah) against acute lymphoblastic leukemia (ALL), and Axicabtagene ciloleucel (Yescarta) against advanced lymphomas like non-Hodgkin lymphoma (NHL). The high success rate in treating blood cell related malignancies with CAR-T cell-based therapy is opening new avenues to use this approach against difficult to treat solid tumors. Currently, USA, Europe, and China are conducting clinical trials in patients with solid tumors like lung cancer, esophageal cancer, breast cancer, colon cancer, bladder cancer, cervical cancer, and glioblastoma. Earlier reports have shown promising results against solid tumors as well and hopes are high that these treatment options will be available in India and very soon.
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