KOCHI: Cancer develops when cells in our body multiply uninhibited. Ageing, lifestyle changes, exposure to toxins — all these factors can stimulate this change. Our immune system has an important role to play in preventing the cells from gaining the ability to proliferate without control and invade other organs by spreading through the bloodstream. And so, patients with diseases like HIV, which cause immunosuppression, have higher chances of developing cancer. The immune system also weakens with age, making elderly people without any risk factors vulnerable to cancer.
Historically, Galen a renowned Greek physician, had documented the relation between immune response and cancer. William Bradley Coley who is known today as the Father of Immunotherapy described cancerous growths disappearing after skin infections. Such spontaneous remissions are extremely rare, happening in 1 out of 60,000- 100,000 cases.
Over the last 100 years, contributions from scientists all over the world were instrumental to understand the fascinating interplay between immune regulation and cancer. In 2018, Nobel Prize was awarded to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets.
Antibody-based therapies were initially used to treat cancer. Antibodies mark out cancer cells. Rituximab, which targets the CD20 antibody on lymphoma cells, became the first monoclonal antibody to be approved in 1997. Over the last 25 years, lakhs of patients across the world were saved using Rituximab alone or by administering it in combination with chemotherapy. Trastuzumab, another monoclonal antibody effective against HER2-receptor expressed in 25 per cent of breast cancers has also improved outcomes in a significant number of patients.
Cancer cells can protect themselves from the immune system by stimulating checkpoints. Checkpoint inhibitors block these points, thus restoring the body’s capacity to fight cancer. In 2011, Ipilimumab was approved for the treatment of Melanoma. In a short span of time, several other inhibitors were approved worldwide. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab all showed significant results in treating cancers including melanoma, cancers of the bladder, lungs and colon.
Targeted use
But these drugs cannot be used for all cancers. For lung cancer, we can measure the PDL1 receptor expression through a biopsy. If the level of expression is over 50 per cent, Pembrolizumab as a single drug is more effective than even chemotherapy. Meanwhile, for lung cancers that lose response to chemotherapy, these drugs can be used irrespective of PD L1 expression. A better understanding of such predictive markers is needed to ensure the most feasible method. Side effects in a fraction of the patients is also a concern. A review of patient records shows that almost 20- 30 per cent of advanced cancer patients who were treated with these drugs survived, compared to less than 5 per cent of historical controls.
Immunosuppressive agents, cytokines, oncolytic viruses and cancer vaccines are being developed to help engineer the immune system better. CART cell therapy involves the isolation of patients’ tumour-specific T-cells in the future. These cells are then modified and multiplied in a laboratory, then reinjected into the patient’s circulatory system. The method showed positive results, especially in leukaemia and lymphoma patients. In the future, immunotherapy drugs may be used more frequently in adjuvant settings to prevent relapse of the disease after curative treatment. Identifying the subset of patients who would benefit the most based on biomarker testing would be the most challenging aspect.
The beginning
The first instance of cancer immunotherapy can be traced to 1891. William Coley, now known as the father of immunotherapy, attempted to treat sarcoma patients.
The author is as senior consultant medical oncologist, Aster Medcity, Kochi