CAR-T Cell Therapy

CAR-T cell therapy (chimeric antigen receptor T-cell therapy) is a cancer treatment in which a patient's own T cells are collected, genetically engineered in a dedicated laboratory to recognise a marker on cancer cells, and returned to the body to attack the cancer. The products available in India target CD19, a marker on B cells, and treat relapsed or refractory B-cell lymphoma and B-cell acute lymphoblastic leukaemia.

For most of the history of haematology, a patient whose lymphoma or leukaemia returned after chemotherapy, or after a bone marrow transplant, faced a narrowing set of options that often ended in palliative care. CAR-T cell therapy changes that arithmetic. Dr. Akash Khandelwal, Consultant Hemato-Oncology & BMT, Fortis Hospital, Shalimar Bagh, New Delhi, India, describes it as a game changer: a treatment that offers a realistic chance of cure to patients for whom little else remained.

This guide sets out what CAR-T is, why it works differently from conventional chemotherapy, how the treatment pathway fits together, and where Dr. Khandelwal expects the field to go over the next decade.

What is CAR-T cell therapy and how does it work?

CAR-T cell therapy works by turning the patient's own immune cells into a targeted treatment. CAR-T stands for chimeric antigen receptor T-cell therapy. It is a cellular therapy, which means the active agent is not a molecule manufactured in a reactor but a population of the patient's own white blood cells, re-engineered to recognise cancer.

The principle has three moving parts:

• The T cell. T cells are the immune system's attack cells. In a patient with relapsed lymphoma or leukaemia, they have failed to control the disease on their own.
• The chimeric antigen receptor (CAR). Using genetic engineering, a synthetic receptor is attached to each T cell. The receptor is built to lock onto one specific marker on the surface of the cancer cell.
• The target. Once the modified cell, now a CAR-T cell, meets a cell carrying that marker, it attacks and kills it.

Dr. Khandelwal frames the result as an immune attack on cancer cells, delivered with the help of a genetically engineered molecule. The patient's own immune system is, in his words, revamped with the help of genetic engineering so that it targets the cancer cell in a unique and different way. That is what makes CAR-T a targeted therapy rather than a broad cytotoxic (cell-killing) one.

He is also direct about how mechanical this can sound on a slide. Take T cells, attach a receptor, return them to the body: it sounds bookish, he concedes, yet it does happen, and it cannot happen just anywhere. The engineering is carried out in dedicated laboratories that follow strict protocols, and that dependence on a specialised manufacturing chain shapes almost every practical feature of the treatment, from its timeline to its cost.

Why CAR-T is made from the patient's own cells

Every CAR-T product currently available is autologous: the T cells are collected from the patient who has the cancer, not from a donor. The consequence for referring clinicians is that the quality of the final product depends on the patient's own T cells. If enough healthy T cells cannot be collected, the treatment cannot proceed. Dr. Khandelwal calls collection the most crucial step in the whole process and the rate-limiting step for CAR-T; how that plays out in practice is covered in the CAR-T cell therapy timeline from collection to recovery.

What does CAR-T target? Why CD19 works today

The CAR-T products commercially available to Dr. Khandelwal's patients are all directed at CD19, a marker carried on B cells. That single design choice explains both the reach and the limits of the therapy today. Cancers of B-cell origin, such as B-cell acute lymphoblastic leukaemia and many B-cell lymphomas, display CD19 and are therefore appropriate targets. Cancers that do not carry a usable target for the existing construct are not. When asked in the masterclass Live Discussion whether CAR-T could be applied to ovarian or cervical cancer, his answer was "not yet": the approach has not yet shown good promise there.

CD19-directed CAR-T is also the version with the deepest evidence base. Dr. Khandelwal points to research from the United States in which a large subset of patients remain in remission after infusion of CD19-targeted cells. That durability, in a population that had already exhausted standard treatment, is the reason the therapy is now in commercial use rather than confined to trials.

When is CAR-T used? Its place in the treatment pathway

Today CAR-T is a treatment for disease that has come back (relapsed) or refused to respond (refractory). It is used where the biology is unfavourable: relapsed or refractory B-cell lymphoma and B-cell acute lymphoblastic leukaemia, including patients who have relapsed after a bone marrow transplant and patients judged unfit for one. The full eligibility picture, the outcome data and how patients access the therapy are set out in who is eligible for CAR-T cell therapy, with outcomes and access.

The practical journey runs from T-cell collection through laboratory manufacture, a short course of conditioning chemotherapy, infusion and a closely monitored recovery. Dr. Khandelwal plans for a minimum of about two months from start to finish, and the step-by-step detail, including complications and their management, is in the timeline article linked above.

Dr. Khandelwal's conclusion is that CAR-T represents a substantial improvement over standard of care. For patients who had lost hope, it converts a palliative trajectory into one with a genuine chance of long-term survival. One of his own patients, who had been offered nothing further where he lived, is now leading a full life after treatment.

Why CAR-T does not cure everyone: persistence and resistance

CAR-T does not cure every patient because the CAR-T cells do not stay in the body for the long term, or the cancer develops resistance to them. Dr. Khandelwal identifies this as the field's most important challenge. Once the engineered cells fade, the disease can return.

Much of current research is therefore aimed at keeping CAR-T cells expanding and active for longer after infusion, to convert good early responses into durable ones.

Next-generation CAR-T: single-target, dual-target and persistence-enhancing designs

The CD19 product is the simplest form of the technology, and Dr. Khandelwal stresses that it is only one point on a broad map. CAR-T already has many categories, classifications and generations:

• Single-target CARs, such as the CD19 constructs in use today, recognise one marker.
• Dual-target CARs recognise two markers rather than one.
• Constructs with additional attachments, which are engineered to make CAR-T cells expand more easily and persist for longer once inside the body, addressing the persistence problem directly.

Dr. Khandelwal gave Burkitt lymphoma as an example of a B-cell cancer not suited to today's products: in his view, the CAR-T construct for it would have to be very different, and the current product would fail. Burkitt lymphoma cells do carry CD19, but the disease is not among the approved indications of the major CD19 CAR-T products, and published experience of CAR-T in it is limited. Each new generation, in his view, will make CAR-T more potent and available for more cancers.

CAR-T beyond lymphoma and leukaemia: myeloma, CLL, AML and solid tumours

The most consequential change ahead is the expansion of CAR-T into cancers outside its current territory. Dr. Khandelwal outlined where the pipeline stands:

• Multiple myeloma is the most advanced. CAR-T for myeloma is already approved in the United States, and Dr. Khandelwal, speaking in March 2025, expected myeloma CAR-T products to become commercially available in India by the end of that year.
• Chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML) have new CAR-T products in phase 1 and phase 2 trials. In chronic lymphocytic leukaemia, a CD19 CAR-T product has been approved in the United States since 2024 for relapsed or refractory disease.
• Paediatric cancers, including Ewing sarcoma, are an active area of development.
• Solid tumours, including brain tumours and kidney cancers, are where he sees a great deal of potential, although the evidence is earlier.

Alongside CAR-T, gene therapy is, as he puts it, knocking at the door. At the time of the session, Fortis Shalimar Bagh was in talks to run a CD19-directed CAR-T clinical trial in lymphoma and leukaemia, which had not yet been approved.

The future of CAR-T cell therapy: from last resort to first line

Within the next five to ten years, Dr. Khandelwal expects CAR-T to become a first-line option in almost all cancers. It is his most striking prediction, because today CAR-T is reserved for relapse. He goes further: if it does not, the field will have missed something, because the ability to target cancer cells in such a different and unique way is too significant to remain a salvage therapy. The data reaching clinicians, he notes, show more and more promise. No CAR-T product is currently approved as a first-line treatment for any cancer.

He expects the economics to move in the same direction. Because every CAR-T dose is still manufactured individually for one patient, the therapy carries a significant cost even where it is among the most affordable in the world. As more data accumulate and more patients are treated, he anticipates definite changes in cost, in potency and in the risk profile of the treatment.

For clinicians across Africa and elsewhere managing patients with relapsed B-cell lymphoma or leukaemia, the implication is immediate rather than futuristic. A patient who would previously have been referred for palliative care may now have a potentially curative option, and because the whole treatment is built from that patient's own T cells, the referral conversation is worth starting before those options narrow further.