CAR T Cell Therapy in India: New Advances in Cancer Care

India is making significant strides in cancer treatment with the introduction of CAR T cell therapy, a cutting-edge approach that harnesses the body’s immune system to fight cancer. This innovative treatment has shown promise for patients with certain blood cancers, offering hope where conventional therapies have failed.

With advancements in local manufacturing and regulatory support, CAR T cell therapy is becoming more accessible within India’s healthcare system.

CAR T Cell Structure And Function

Chimeric Antigen Receptor (CAR) T cells are genetically engineered immune cells designed to recognize and eliminate cancerous cells. These modified T cells carry a synthetic receptor that binds to target antigens on malignant cells. Unlike conventional T cells, which rely on major histocompatibility complex (MHC) molecules for antigen recognition, CAR T cells function independently of MHC, allowing them to target tumors that evade immune detection.

A CAR consists of an extracellular antigen-binding domain, a transmembrane region, and an intracellular signaling domain. The antigen-binding domain, typically derived from a single-chain variable fragment (scFv) of a monoclonal antibody, provides specificity for tumor-associated antigens such as CD19 in B-cell malignancies. The transmembrane domain anchors the receptor to the T cell membrane, ensuring stability. The intracellular signaling domain activates the T cell upon antigen engagement, triggering cytotoxic activity and cytokine release. Later-generation CARs incorporate co-stimulatory domains such as CD28 or 4-1BB to enhance proliferation, persistence, and therapeutic efficacy.

CAR T cells expand rapidly upon antigen recognition, forming a population of effector cells capable of sustained activity. This expansion allows for prolonged immune surveillance, with some CAR T cells exhibiting memory-like properties that provide long-term protection against relapse. However, their function can be affected by antigen density, the tumor microenvironment, and exhaustion markers. Strategies to improve persistence, such as modifying metabolic pathways or incorporating cytokine support, are being explored to enhance durability and reduce relapse rates.

Key Phases Of Manufacturing In Indian Facilities

The manufacturing of CAR T cells in India involves a multi-step process to generate highly potent, patient-specific therapeutic cells. It begins with the collection of autologous T cells from the patient through leukapheresis, a procedure that isolates white blood cells while returning other blood components. Maintaining cellular viability during this stage requires optimized anticoagulants and controlled transport conditions. Given India’s geographic diversity, specialized cryopreservation techniques stabilize cells before processing.

At the manufacturing site, T cells undergo activation and genetic modification using viral vectors like lentiviruses or retroviruses, which integrate the CAR construct into the T cell genome. Lentiviral vectors are preferred for their ability to transduce non-dividing cells and maintain stable gene integration. Indian manufacturing centers are optimizing vector production protocols to ensure high titers and sterility while adhering to biosafety regulations. The transduced T cells are then expanded under controlled bioreactor conditions, with cytokine supplementation such as IL-2 or IL-15 to support proliferation and prevent exhaustion.

Each batch of CAR T cells must meet rigorous potency, purity, and safety benchmarks before infusion. Flow cytometry verifies CAR expression levels, while functional assays assess cytotoxic activity. Sterility testing ensures the absence of microbial contamination, a critical step given the immunosuppressive nature of many cancer patients. Indian facilities are integrating rapid-release testing methodologies, such as real-time PCR for replication-competent virus detection, to streamline approval without compromising safety.

Collaborations Between Healthcare Centers

The success of CAR T cell therapy in India depends on collaborations between healthcare institutions, research laboratories, and biotechnology firms. Leading cancer centers are forming alliances to pool expertise, optimize workflows, and ensure seamless patient care. These partnerships integrate advanced cellular engineering techniques with clinical oncology, improving patient selection, treatment administration, and post-infusion monitoring.

One key initiative is the establishment of centralized cell processing units serving multiple hospitals. Instead of each institution developing its own manufacturing facility, hospitals partner with specialized biomanufacturing centers for CAR T cell production. This model standardizes quality control and accelerates the turnaround time from leukapheresis to infusion. Shared biorepositories for cryopreserved T cells ensure sample viability despite logistical delays, benefiting regions with limited access to high-end laboratory equipment.

These partnerships also support clinical trial execution and patient recruitment. Multi-center trials enhance data collection, refining treatment protocols for different cancer subtypes. Indian hospitals are increasingly participating in global CAR T cell therapy trials, collaborating with international research consortia to align methodologies with best practices. Knowledge exchange through joint training programs further strengthens the expertise of oncologists and immunologists handling CAR T cell therapy.

Common Cancer Types Addressed

CAR T cell therapy has shown significant efficacy in treating hematologic malignancies, particularly resistant cases. One of its most well-established applications is in B-cell acute lymphoblastic leukemia (B-ALL), a rapidly progressing blood cancer affecting children and young adults. Targeting CD19, a surface antigen on malignant B cells, has resulted in complete remission rates exceeding 80% in relapsed or refractory cases, offering an alternative for patients who have exhausted chemotherapy or bone marrow transplant options.

Beyond B-ALL, CAR T cell therapy has been instrumental in treating B-cell non-Hodgkin lymphomas (B-NHL), including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). CAR T cell products like axicabtagene ciloleucel and tisagenlecleucel have significantly improved survival outcomes. Studies show that many relapsed or refractory DLBCL patients achieve durable remissions, with some remaining disease-free beyond five years. This durability is particularly promising given the aggressive nature of relapsed B-NHL, where median survival with traditional salvage therapies is often less than a year.

Regulatory Aspects And Authorization

The introduction of CAR T cell therapy in India has required robust regulatory frameworks to ensure patient safety and treatment efficacy. Regulatory bodies such as the Central Drugs Standard Control Organization (CDSCO) and the Indian Council of Medical Research (ICMR) have developed guidelines for clinical trials, manufacturing, and commercialization. These regulations align with global standards, incorporating insights from agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The approval process includes rigorous preclinical evaluations, phased clinical trials, and post-marketing surveillance to monitor long-term outcomes and adverse effects.

A major regulatory challenge is balancing expedited approvals with comprehensive safety assessments. Given the life-threatening conditions CAR T cell therapy targets, accelerated pathways have been introduced for promising investigational therapies. However, ensuring manufacturing consistency and adherence to good manufacturing practices (GMP) remains a priority. Regulatory agencies require detailed documentation on vector production, cell expansion protocols, and quality control measures before approval. Pharmacovigilance programs track potential adverse events such as cytokine release syndrome (CRS) and neurotoxicity, ensuring healthcare providers can manage complications effectively. These measures are critical in fostering public trust and expanding access to CAR T cell therapy in India.

Patient Referral Process

The patient referral process for CAR T cell therapy in India requires coordination between oncologists, hematologists, and specialized treatment centers to ensure appropriate patient selection. Referrals are typically limited to patients with relapsed or refractory hematologic malignancies who meet specific eligibility criteria. Physicians assess disease stage, prior treatment history, and overall health status, as factors such as organ function and disease burden influence therapeutic success. Multidisciplinary tumor boards are increasingly reviewing cases to determine eligibility.

Once a patient is deemed eligible, logistical considerations such as leukapheresis scheduling, manufacturing timelines, and hospital admission planning come into play. Given the time-sensitive nature of the therapy, referral networks facilitate communication between local oncologists and specialized CAR T cell centers, ensuring patients from remote or underserved regions can access treatment without delays. Financial counseling is often integrated into the referral process, as the high cost of CAR T cell therapy necessitates discussions on insurance coverage, government funding programs, or clinical trial enrollment options. By refining the referral pathway, India’s healthcare system is working toward making this advanced therapy more accessible.