AIIMS and Delhi develop low-cost adaptive cell therapy to treat multiple myeloma

(CAR) T-cell therapy is a form of adaptive cell therapy in which a patient’s T cells are isolated, genetically modified, and reinfused back into the patient to recognize and kill cancer cells. Photos are for representative purposes only | Photo credit: Freepik

Doctors at Delhi’s AIIMS are developing a low-cost, antibody-based adaptive cell therapy to treat multiple myeloma, a blood cancer.

This therapy is expected to make advanced therapies such as CAR-T cell therapy more affordable for Indian patients.

Chimeric Antigen Receptor (CAR) T-cell therapy is a form of adaptive cell therapy in which a patient’s T cells are isolated, genetically modified and reinfused back into the patient to recognize and kill cancer cells, researched by Dr. BR Ambedkar, AIIMS Department of Medical Oncology, Rotary Cancer Hospital (BRAIRCH).

It is based on targeting B-cell maturation antigen (BCMA), which helps target specific tumor antigens found in cancer cells, especially in cases of multiple myeloma. “As a result, AIIMS researchers developed therapies that target BCMA in multiple myeloma cells to eliminate them,” said Dr. Singh.

So far, the therapy has been tested on animal models and shown promising results, he said.

“We intend to move this CAR-T cell therapy into human Phase 1 clinical trials in the near future to collect substantial evidence on its safety and efficacy. Our goal is to significantly reduce the cost of this therapy. There are others forms of CAR-T cell therapy, but the cost of these therapies is very high,” he said.

How do cancer cells work?

Cancer is characterized by uncontrolled growth of cancer cells. Dr. Singh explained that generally, all cancer cells originate from a single cell that undergoes a series of mutations that transform it into cancer cells, which are involved in the different symptoms associated with cancer.

Cancer cells proliferate at very rapid rates, depriving normal cells of nutrients, leading to cancer-related cachexia.

What is multiple myeloma?

Multiple myeloma is a cancer of plasma cells, a type of white blood cell (WBC) that produces infection-fighting antibodies. When these cells become cancerous, they multiply rapidly and crowd out normal blood-forming cells in the bone marrow. Dr. Singer said this form of cancer is often associated with recurrence.

Traditional cancer treatments such as chemotherapy/radiation therapy target rapidly dividing cells, but this approach causes cytotoxicity of normal cells and leads to serious side effects associated with cancer treatment.

The emergence of targeted cancer therapies over the past two decades has been associated with targeting inherent vulnerabilities of cancer cells, such as their overreliance on one protein, which have improved cancer treatment outcomes. However, he explained, cancer cells eventually become resistant to these drugs, causing the cancer to come back.

Over the past decade, the emergence of immunotherapy, in which monoclonal antibodies are used to target cancer cells, has also become one of the cornerstones of cancer treatment.

In the classic approach, these antibodies against cancer targets are often loaded with drugs of interest for targeted delivery of chemotherapy drugs, thereby reducing off-target effects and increasing their effectiveness, Dr. Singer said.

“Antibody-based therapies have ushered in a new era of cancer treatment, including the development of cellular CAR-T cell therapies, which include components of these antibodies to target antigens on cancer cells. However, immunotherapies remain expensive and therefore not suitable for most It is out of reach for people in countries like India,” he explains.

One in nine people in India may develop cancer in their lifetime

According to the latest data from the National Cancer Registry, the number of cancer cases in India is expected to be 14,61,427 in 2022. Additionally, one in nine people is likely to develop cancer in their lifetime.

Dr. Singh said the problem of delayed diagnosis coupled with limited access to world-class therapies is bound to create a huge health burden in India as cases are expected to grow exponentially over the next decade.

The research team led by Dr. Singh has applied for an Indian patent for the antibody and is in the process of applying for a patent for its CAR-T cell therapy.

“CAR-T cell therapy has changed the way we approach and treat cancer. Although CAR-T cell therapy is developing rapidly globally, it is still in its infancy in India.