Paradigm Shifts In Cancer Treatment: From Immunotherapy To CAR-T & Beyond

Cancer continues to be a major global health concern, with its incidence and prevalence continuing to rise. As of 2024, the World Health Organization (WHO) estimates that over 19 million new cancer cases occur annually, with over 10 million cancer-related deaths. The prevalence of cancer is increasing due to a combination of ageing populations, unhealthy lifestyle changes, better cancer detection methods, and also improved survival of patients with cancer. 

Conventional chemotherapy has been in use for cancer treatment for a long time. It has benefits and drawbacks. Advantages of systemic chemotherapy include its ability to kill rapidly dividing cancer cells throughout the body, making it effective against a wide range of cancers. However, its non-selective nature also targets healthy cells, leading to adverse effects like nausea, hair loss, and weakened immune function. Its efficacy may vary, in various cancers, but it continues to play a crucial role in cancer care, often used in combination with other therapies for optimal outcomes.

Evolving Cancer Treatment: Beyond Conventional Chemotherapy

The treatment of cancer is continuously evolving, it is driven by advances in research and technology. Immunotherapy is a significant breakthrough in this quest that has shown remarkable success in certain cancers. It works by leveraging the body’s immune system to target cancer cells more precisely, offering a more targeted approach. Among the most promising forms of immunotherapy are checkpoint inhibitors, which block proteins that prevent immune cells from attacking cancer cells. However, the limitations of conventional immunotherapies, such as non-specific targeting and limited efficacy in some cancer types, have prompted the exploration of more sophisticated approaches. This is where the research is exploring other therapies like Bispecific T-cell engagers (BiTEs) and cellular therapies like CAR T-cell therapy.

Bispecific T-cell engagers (BiTEs) are transforming cancer care by harnessing the immune system's power to target and eliminate cancer cells. These engineered antibodies simultaneously bind to immune T-cells and cancer cells, effectively bringing them together and triggering the immune response to destroy the cancer. BiTEs, such as blinatumomab, have shown impressive results in treating certain blood cancers, particularly acute lymphoblastic leukaemia. The success rate of BiTEs in hematologic malignancies is driving research into their application for solid tumours. This innovative approach offers a more targeted and potent treatment option, reducing side effects and improving outcomes for cancer patients.

Another innovative approach in cancer care is CAR-T cell therapy, where a patient's T cells are modified to better recognize and destroy cancer cells. CAR T-cell therapy involves extracting a patient's T cells, genetically engineering them to express chimeric antigen receptors (CARs) that specifically target cancer cells, and then infusing these modified cells back into the patient. These engineered T cells are highly specific and are able to recognize, attack, and destroy cancer cells with precision, leading to significant clinical responses, especially in hematologic malignancies like certain leukaemias and lymphomas. Emerging therapies like tumour-infiltrating lymphocyte (TIL) therapy and dendritic cell vaccines are also showing promise. The success of CAR T-cell therapy has been groundbreaking, demonstrating high remission rates in patients with otherwise refractory cancers. However, there are challenges such as cytokine release syndrome, neurotoxicity, and manufacturing complexities that need to be addressed to broaden the applicability and safety of CAR T-cell therapies. We also need to work on the affordability issues for widening access to more deserving patients in our country.

We are now moving into the era of Precision medicine which tailors therapies based on genetic profiles, enhancing effectiveness, and reducing toxicity. Advances in gene editing and stem cell research are paving the way for more precise and effective cancer treatments. These innovative approaches are expanding the therapeutic arsenal, offering hope for more personalised, effective, and less toxic cancer treatments in the future improving survival rates and quality of life.

The author is a Consultant - Haematologist, Haemato Oncologist, & Bone Marrow Transplantation Physician-Manipal Hospital 

Dr. Mallikarjun Kalashetty

Guest Author