Chimeric Antigen Receptor T-cell (CAR-T) therapy

9-Feb-2023: CAR T-Cell Therapy gets global attention

CAR T-Cell Therapy:

A new Systemic Therapy for Cancer Treatment that uses patients' own cells modified in a laboratory to activate T-cells and target tumor cells.
Approved for leukaemias and lymphomas

Procedure:

T cells are taken from a patient’s blood
Gene for a special receptor (CAR) that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory
Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion

Significance:

More specific than targeted agents
Directly stimulate the patient's immune system to fight cancer
Greater clinical efficacy
Referred to as "living drugs"

Chemotherapy

Attacks fast-growing cancer cells.
Has significant side effects due to affecting many types of cells in the body.

Targeted agents/Immunotherapy

Binds to specific targets on the cancer or immune cells supporting its growth.
Less toxic as it affects fewer non-tumor cells.
Works only on tumors that have these targets.

Challenges:

Preparation:

Difficulty in preparing CAR T-cell therapies
First successful clinical trial published a decade ago
First indigenously developed therapy in India performed in 2021

Side Effects:

Efficacy varies in different types of cancers
There are significant potential side effects such as,
- Cytokine release syndrome
- Neurological symptoms

Affordability:

Cost and value concerns
Critics argue that it may still be unaffordable for most people

T Cells:

Type of white blood cell
Play a central role in the immune response
Involved in cell-mediated immunity
Help the body recognize and respond to foreign substances, such as viruses, bacteria, and abnormal cells, such as cancer cells

Two major types:

Helper T cell - Helps other cells of the immune system.
Cytotoxic T cell - Kills virally infected cells and tumors.

2021

8-Jun-2021: Department of Biotechnology supported First CAR-T cell therapy conducted at ACTREC, Tata Hospital in Mumbai

The Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a breakthrough in cancer treatment. Clinical trials conducted globally have shown promising results in end stage patients, especially in patients suffering from Acute Lymphocytic Leukemia. Though this technology has a remarkable therapeutic potential for cancer patients, at present this technology is not available in India. Each patient's CAR-T cell therapy costs 3-4 crore (INR). The challenge therefore is to develop this technology in cost-effective manner and make it available for the patients.

The manufacturing complexity is a major reason for the therapy cost. In order to promote and support development of CAR-T cell technology against cancer and other diseases, BIRAC and DBT have taken initiatives and launched specialized calls to invite proposals in the last 2 years.

The 4th June, 2021 was a historic day for TMH, IIT Bombay team and cancer care in India as the first CAR-T cell therapy (a type of gene therapy) was done at the Bone Marrow Transplant unit at ACTREC, Tata Memorial Center in Mumbai. The CAR-T cells were designed and manufactured at Bioscience and Bioengineering (BSBE) department of IIT Bombay.

This work is partly supported by BIRAC-PACE scheme. The TMC-IIT Bombay team are further supported to extend this project for conducting Phase I/II trial of their CAR-T product by DBT/BIRAC, through National Biopharma Mission.

This is a “first in India” gene therapy in early phase pilot clinical trial and the dedicated efforts and excellent collaboration between IIT Bombay and Tata Memorial Hospital, Mumbai. The central government’s National Biopharma Mission-BIRAC has approved 19.15 Cr crore to the team for conducting a first-in-human phase-1/2 clinical trial of the CAR-T cells. The clinical trials are being done by Dr (Surg Cmdr.) Gaurav Narula, Professor of Paediatric Oncology and Health Sciences, and his team from TMC, Mumbai, and the novel CAR-T cells that will act as drugs that were manufactured by Prof Rahul Purwar, Bioscience and Bioengineering (BSBE) department and his team at IIT Bombay. The design, development, and extensive pre-clinical testing was carried out by IIT-B as a collaborative project with Tata Memorial Center, Mumbai by the two Investigators.

IIT-B director Subhasis Chaudhuri said this was a significant feat for the institute as well as the country. “We at IIT-B are delighted that our scientists along with Tata Memorial Hospital have come out with the most sophisticated therapy in cancer treatment. If the trials are successful, it may save millions of lives by making the treatment available in India at an affordable cost. It is a research of IIT-B that is expected to touch the lives of all,” said Chaudhuri.

National Biopharma Mission is also supporting the development of Lentiviral vector manufacturing facility for packaging plasmids used to transfer the modified T cell inside the body, cGMP facility for T-cell transduction and expansion for CAR T-cell manufacturing to two other organizations. The development of CAR-T cell technology for diseases including acute lymphocytic leukemia, multiple myeloma, glioblastoma, hepatocellular carcinoma and type-2 diabetes is supported through DBT.

About DBT: The Department of Biotechnology (DBT), under the Ministry of Science & Technology, promotes and accelerates the development of biotechnology in India, including growth and application of biotechnology in the areas of agriculture, healthcare, animal sciences, environment and industry.

About BIRAC: Biotechnology Industry Research Assistance Council (BIRAC) is a not-for-profit Section 8, Schedule B, Public Sector Enterprise, set up by Department of Biotechnology (DBT), Government of India as an Interface Agency to strengthen and empower the emerging Biotech enterprise to undertake strategic research and innovation, addressing nationally relevant product development needs