CAR T-cell Therapy

What is CAR T-cell therapy?

Chimeric Antigen Receptor (CAR) T-cell is modern immunotherapy intended to improve the body’s immune response to cancer cells. It entails the alteration of a patient’s T cells to be able to identify and target more cancerous cells. This therapy has been successful in addressing some sort of blood cancer thereby providing a ray of hope for patients who have tried other forms of treatment without avail.

CAR T-cell therapy for cancer

CAR T-cell therapy (Chimeric Antigen Receptor T-cell therapy) is a pioneering and customized type of immunotherapy for the treatment of some cancers. It utilizes the patient's own immune system—T-cells—to recognize and destroy cancer cells.

Key Reasons for CAR T-Cell Therapy:

Treatment-Resistant Cancers

• Leukemia and lymphoma are kinds of blood cancers for which resistance to conventional treatments is sometimes inevitable, and thereby, CAR T-Cell therapy matters.

Relapsed Cancers

• Those who develop cancer again after the first line of therapy require another or more effective line of therapy.

Lack of Other Effective Options

• However, for patients who cannot undergo bone marrow transplants or who have no other treatment choices, the CAR T-cell therapy can be a chance to save their life.

Personalized & Long-Lasting Treatment

• CAR T-cells are persistent in the body and monitor the body for any relapse of the cancer cells.

Higher Success Rates in Some Blood Cancers

• Research has it that a high rate of remission is realized, more especially if the disease is Acute Lymphoblastic Leukemia (ALL) and Diffuse Large B-Cell Lymphoma (DLBCL).

Potential Expansion to Other Cancers

• The development of CAR T-cell therapy is still active for solid tumors such as breast, lung, and brain tumors and other autoimmune diseases.

CAR T-cell therapy is mainly applied to treat blood cancer, including:

• Acute Lymphoblastic Leukemia (ALL) – Most effective in pediatric and young adult patients.
• Diffuse Large B-Cell Lymphoma (DLBCL) – A common and aggressive form of non-Hodgkin lymphoma.
• Mantle Cell Lymphoma (MCL) - A rare but challenging to cure lymphoma.
• Multiple Myeloma – New CAR T therapies that have recently been developed has been reported to be effective.

Factors Affecting CAR T-cell therapy cost

Several factors contribute to the high cost of CAR T-cell therapy. Below is a breakdown of the key factors affecting CAR T-cell therapy cost, both globally and in India:

• Personalized Cell Engineering
• Hospitalization and Supportive Care
• Pre-treatment & Post-treatment Therapies
• Managing Adverse Effects
• Type of Cancer & Therapy Brand
• Location of Treatment
• Regulatory and Licensing Costs
• Expertise and Multidisciplinary Team

CAR T-cell therapy success rate

The rate of success with CAR T-cell therapy varies based on various factors such as the nature of cancer, stage of disease, patient well-being, and respective CAR T product applied. CAR T-cell therapy has been highly successful in blood cancers where other therapies have failed.

• B-cell Acute Lymphoblastic Leukemia (ALL): 80–90%
• Diffuse Large B-cell Lymphoma (DLBCL): 50–80%
• Mantle Cell Lymphoma (MCL): 85–90%
• Multiple Myeloma: 70–95%

How does CAR T-cell therapy work?

• T-Cell Collection: The patient’s blood sample is taken through a process called Leukapheresis for collection of T cells that is one kind of Immune cells.
• Genetic Modification: In the act of genetic modification, T cells are transduced with a unique receptor known as Chimeric Antigen Receptor. This receptor enables T cells to detect the existing cancer cells and go in for an attack.
• Proliferation: The T cells are set asexually to produce millions of T cells with modified receptors.
• Infusion to the Patient: The patient is given a short chemotherapy regimen before the modified T cells are re-infused for infusion back into the patient’s bloodstream.
• Killing Cancer Cells: After entering the body, the CAR T-cells are programmed to attack cancer cells and have been known to result to remission.

CAR T-cell therapy side effects

CAR T-cell therapy is highly effective against cancer, but it also produces severe and potentially fatal side effects. They are a consequence of the vigorous activation of the immune system when CAR T-cells target cancer cells. Some side effects are frequent but tolerable, whereas others necessitate hospitalization or intensive care.

Cytokine Release Syndrome (CRS)

• Most frequent and severe side effect
• Seen in up to 90% of patients (mild to severe)
• What it is: Systemic inflammatory response due to massive cytokine release by activated T-cells.

Symptoms:

• Fever
• Low blood pressure (shock)
• Rapid heart rate
• Shortness of breath
• Organ dysfunction (in severe cases)
• Onset: 1–14 days following infusion

Management:

• Tocilizumab (IL-6 receptor blocker)
• Corticosteroids
• ICU management in severe cases

Neurotoxicity (ICANS – Immune effector Cell-Associated Neurotoxicity Syndrome)

• Incidence in 20–60% of patients
• What it is: Inflammation of the brain due to immune activation.

Symptoms:

• Confusion, disorientation
• Slurred speech
• Headache
• Seizure
• Brain swelling (rare but life-threatening)
• Onset: Typically 4–10 days after infusion

Management:

• Steroids (such as dexamethasone)
• Supportive care, occasionally ICU

B-cell Aplasia / Hypogammaglobulinemia

• What it is: CAR T-cells that destroy CD19 also destroy healthy B-cells.
• Symptoms: Higher risk of infection due to low antibodies.

Management:

• Regular IVIG (Immunoglobulin) infusions
• Long-term monitoring for infection

Infections

• Due to low white blood cell count and compromised immune system.
• Common infections: Respiratory, viral, bacterial, fungal.

Prevention:

• Antibiotic/antiviral prophylaxis
• Close monitoring after therapy

Organ Toxicity

Less frequent but potential effect on:

• Liver (raised enzymes)
• Kidney (temporary impairment)
• Heart (low blood pressure or arrhythmia)
• Associated with severe CRS or pre-existing conditions.

Fatigue & Overall Side Effects

A. Mild symptoms are:

• Fatigue
• Muscle pains
• Loss of appetite

B. Transient decreased blood counts

• Typically resolve in weeks.

CAR T-cell therapy for leukemia

CAR T-cell therapy has been spectacularly successful with some forms of leukemia, especially in patients with relapse or resistance to standard treatments. It is now most useful for B-cell Acute Lymphoblastic Leukemia (B-ALL).

How It Works in Leukemia?

CAR T-cell therapy is a process where a patient's own T-cells are altered to bear chimeric antigen receptors (CARs) that bind to CD19, a protein on the surface of the majority of B-cell leukemia cells. When infused, the CAR T-cells find and kill the leukemia cells.

CAR T-cell therapy for lymphoma

CAR T-cell therapy has transformed the treatment of relapsed or refractory B-cell lymphomas to provide an even curative option after several previous treatments have failed. It is approved by the FDA and increasingly available in India via clinical trials and specialized cancer facilities.

How It Works

• T-cells are harvested from the patient through apheresis.
• The T-cells are engineered in a laboratory to generate chimeric antigen receptors (CARs) for the recognition of CD19, a B-lymphoma cell protein.
• Once pre-conditioned with chemotherapy, the CAR T-cells are re-infused back to eliminate lymphoma cells.

Latest advances in CAR T-cell therapy

• CAR T-cell therapy continues to move at breakneck speed, pushing beyond blood cancers, enhancing safety, and opening up off-the-shelf options. Here are the major latest breakthroughs that are shaping the future of CAR T therapy:

Next-Generation CAR T-Cell Designs

Dual/Multitarget CARs

• Binds to multiple antigens (e.g., CD19 + CD22 or CD19 + CD20) to prevent cancer relapse.
• Aids in overcoming tumor antigen escape, a significant reason for treatment failure.

Armored CAR T-cells

• Engineered to produce cytokines such as IL-12 or IL-15, increasing persistence and efficacy.
• Can combat more aggressive tumor microenvironments (particularly solid tumors).

Logic-gated CARs

• Employ AND/OR/NOT logic circuits to render CAR T-cells more specific in attacking tumor cells without damaging normal tissue.
• Example: Attacking tumor-specific combinations of antigens.

CAR T for Solid Tumors

In the past, CAR T-cell therapy was most effective against blood cancers, but new studies are extending into solid tumors, including:

Glioblastoma

• EGFRvIII, IL13Rα2
• Early trials

Pancreatic Cancer

• Mesothelin, Claudin-18.2
• Phase I–II

Ovarian/Breast

• MUC1, HER2, folate receptor α
• Current

Colorectal

• CEA, NKG2D ligands
• Investigational

Allogeneic ("Off-the-Shelf") CAR T-Cells

• Donor-derived CAR T-cells, engineered to prevent immune rejection and graft-versus-host disease (GVHD).
• Examples: ALLO-501, UCART19, and CyCART-19.

Key advantages:

• Ready-to-use (no delay for patient cell collection)
• Reduced cost and speed of treatment
• In Phase I/II trials currently, initial results encouraging.

CAR-NK and CAR-Macrophage Therapies

• CAR-NK cells (Natural Killer cells): Less toxic, with reduced CRS risk and no GVHD.
• CAR-Macrophages: Enhance immune system's cancer cell-eating power and trigger wider anti-tumor response.
• These could supplement CAR T therapy or provide stand-alone options.

Enhanced Safety Switches and Control Systems

To control severe side effects (such as CRS and neurotoxicity) better:

• "Safety switches" such as inducible caspase-9 enable physicians to switch off CAR T-cells in case of toxicity.
• Regulatable CARs controlled by small molecules to modulate T-cell function in real-time.

Developments in India (2024–2025)

• NexCAR19 (first indigenous Indian CAR T-cell product) is in late-stage clinical trials for CD19+ B-cell leukemias.
• Designed by ImmunoACT (spin-off from IIT Bombay) in collaboration with Tata Memorial Centre.
• Indian scientists are also pursuing dual-target CARs and solid tumor platforms.

AI and Genomic Tools in CAR T Development

• AI-guided antigen discovery identifies new, cancer-specific antigens.

Single-cell RNA sequencing and CRISPR screening are applied to:

• Improve CAR T effectiveness
• Predict resistance
• Personalize treatment

Immunotherapy vs CAR T-cell therapy

Immunotherapy

• Immunotherapy is a general category of treatment that stimulates or re-establishes the body's own immune response to recognize and kill cancer cells. 
• Examples of such therapies are immune checkpoint inhibitors (such as PD-1 or CTLA-4 blockers), monoclonal antibodies, and cancer vaccines. 
• These methods allow the immune system to recognize and attack the cancer either indirectly or by augmenting the immune responses that are already there.
• Immunotherapy is applied extensively to solid tumors like lung cancer, melanoma, kidney cancer, and bladder cancer, as well as to some blood cancers. 
• It is increasingly being used earlier in the treatment and can be used together with chemotherapy, radiation, or surgery.
• Immunotherapy tends to be successful in 20–40% of patients, but when it is, it results in lasting remissions, especially in melanoma and non-small cell lung cancer. 
• Not all patients will respond, though, and which patients will be successful is being researched.
• Side effects of immunotherapy tend to resemble autoimmune disease, since the immune system can strike normal organs. 
• Sking rash, diarrhea, thyroid dysfunction, and lung or liver inflammation are common. These are typically controlled with steroids or other immunosuppressants.

CAR T-cell Therapy

• CAR T-cell therapy, however, is a highly personalized and targeted immunotherapy. 
• It entails the collection of a patient's T-cells and engineering them in a lab to produce chimeric antigen receptors (CARs) that directly recognize and target cancer cells. 
• These engineered cells are then returned to the patient, where they hunt for particular antigens (e.g., CD19) on cancer cells and kill them.
• CAR T-cell treatment is best suited for currently relapsed or refractory blood malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and multiple myeloma. 
• Its application in solid tumors remains under initial clinical investigation and not yet widely effective.
• CAR T-cell therapy provides extremely high rates of response—frequently 50–90% in blood malignancies for which other agents have not worked. 
• Complete remissions are often achieved by many patients, and in a few instances, the response is lasting for several years following one treatment.
• CAR T-cell therapy has a different risk profile, primarily Cytokine Release Syndrome (CRS) and neurotoxicity (ICANS). CRS produces high fever, low blood pressure, and organ dysfunction. 
• Neurotoxicity can produce confusion, seizures, or swelling of the brain. These have to be monitored closely, usually in ICU, and need special treatment such as tocilizumab.

Why Choose GetWellGo for CAR T-cell Therapy?

GetWellGo is regarded as a leading supplier of healthcare services. We help our foreign clients choose the best treatment locations that suit their needs both financially and medically.

We offer:

• Complete transparency
• Fair costs.
• 24 hour availability.
• Medical E-visas
• Online consultation from recognized Indian experts.
• Assistance in selecting India's top hospitals for CAR T-Cell Therapy.
• Expert oncologist with a strong track record of success
• Assistance during and after the course of treatment.
• Language Support
• Travel and Accommodation Services
• Case manager assigned to every patient to provide seamless support in and out of the hospital like appointment booking
• Local SIM Cards
• Currency Exchange
• Arranging Patient’s local food