Researchers have developed a groundbreaking in vivo CAR-T cell therapy that reprograms immune cells directly inside the body using mRNA, eliminating the need for lab-based manipulation known as In vivo CAR T-cell generation

How does In vivo CAR T-cell generation work?

• Researchers engineered CAR T-cells directly in the body using mRNA + lipid nanoparticles (LNPs).

• LNPs carry mRNA with CAR instructions and are targeted to CD8+ T cells using specific antibodies.
• Once infused into bloodstream:
  • T cells absorb mRNA
  • Temporarily express CAR
  • Seek & destroy target B cells (e.g. CD19+, CD20+)

What is CAR-T cell therapy?

• CAR T Cell is a novel and highly complex immune therapy that redirects the body’s immune system to fight cancer. 

• CAR-T cells are often described as ‘the living drug’ because they actively search and target malignant cells.
• Principle: It uses a type of immune cell called a T-cell, which is extracted from a patient’s blood before being genetically altered to allow it to target surface proteins found on cancer cells.
• Mechanism: The patient’s T-cells (types of immune cells) are collected and genetically modified into potent cancer fighters known as CAR-T cells. 
• The genetically modified cells express chimeric antigen receptors (CARs) specific to cancer cells. 
• The modified CAR-T cells are then expanded in the laboratory before being infused into the patient. 
• Once in the body, these engineered cells recognise and attack cancer cells, with a focus on B-cell cancers, thus offering a targeted and potent immunotherapy.

Why is CAR T Cell therapy effective?

• Improves immunogenic memory, which provides continuous surveillance to treat local and distant metastatic lesions.
• Recognises and eliminates damaged cells and cells infected with harmful pathogens, such as viruses and cancerous cells.
• Reduces the need for aggressive chemotherapy and Bone transplantation.
• Affordability: Indigenous CAR-T cell therapy brings treatment costs down from Rs 4 crore to Rs 40 lakh.
• Success Rate: In studies, 9 out of 10 people with acute lymphoblastic leukemia whose cancer didn’t respond to other treatments or whose cancer came back had complete remission with CAR T cell therapy.
  • Remission means the cancer can’t be detected in tests.

Significance of  in vivo CAR-T cell therapy

• Conventional CAR T (India): ₹60–70 lakh (~₹30–35 lakh for cell processing)
• New method advantages:
  • No specialised cell manufacturing — reduces cost and complexity
  • Avoids chemo-based lymphodepletion — lowers infection risk, shortens hospital stay
  • Safer for frail, elderly, or comorbid patients.
• India has high incidence of B-cell driven cancers like:
  • Diffuse large B-cell lymphoma  (34–60% of non-Hodgkin lymphoma)
  • Acute lymphoblastic leukemia (75% of childhood cancers)

Limitation

• Still preclinical — human trials pending.

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