TECHNIQUE TO MAKE CAR T-CELLS IN VIVO : BREAKTHROUGH IN CANCER IMMUNOTHERAPY

Why is News : 

  • A June 2024 Science journal study proposes a novel in vivo CAR T-cell therapy technique, where genetic reprogramming of immune cells happens directly inside the body—without lab-based cell extraction.
  • If successful, this could revolutionize cancer and autoimmune disease treatment, especially in resource-constrained nations like India.

What Is CAR T-Cell Therapy?

  • CAR (Chimeric Antigen Receptor) T-cell therapy is a form of immunotherapy that trains T-cells to recognize & destroy cancer cells.
  • In the traditional method, T-cells are extracted from the patient, genetically modified in a lab (usually using viral vectors), and reinfused after chemotherapy.
  • Used in aggressive blood cancers (e.g. Acute Lymphoblastic Leukemia, Non-Hodgkin Lymphoma) and being explored for autoimmune diseases like lupus.

Limitations of Conventional CAR T-Cell Therapy

  • Requires ex vivo processing and custom viral engineering.
  • Involves toxic chemotherapy to prepare the immune system.
  • Costs ₹60–70 lakh in India, with ~₹35 lakh for cell manufacturing.
  • Risk of cytokine storm, neurological effects, and immunodeficiency post-treatment.

The In Vivo Technique (CD8-tLNP Approach)

What’s new?

  • mRNA is packaged in CD8-targeted lipid nanoparticles (CD8-tLNP) and injected into the bloodstream.
  • These nanoparticles deliver CAR-encoding RNA directly to CD8+ T cells, converting them into cancer-fighting agents inside the body.

Advantages:

  • No need for cell extraction or lab modification.
  • Avoids viral vectors — reducing long-term genetic risks.
  • Bypasses chemotherapy, reducing hospital stays and infection risk.
  • Delivery resembles a drug infusion, not complex cell therapy.

Results from Animal Trials

In mice and monkeys, the technique:

  • Reprogrammed up to 85–95% of T-cells to target cancer.
  • Led to tumour regression and B-cell depletion across organs.
  • Used Lipid 829, a biodegradable carrier with low inflammation risk.

Safety Concerns

  • Most animals tolerated treatment well with minor inflammation.
  • One monkey developed an immune overreaction (HLH), highlighting the need for clinical dose control.
  • Human trials are pending to evaluate safety, repeatability, and long-term effects.

Relevance for India

India has a high burden of:

  • DLBCL (34–60% of Non-Hodgkin lymphoma cases)
  • Acute lymphoblastic leukaemia (75% of childhood cancers)
  • Rising autoimmune disorders post-COVID (↑30%)

Current CAR T-cell therapy is:

  • Unaffordable for most
  • Limited by infrastructure (few cell therapy labs)

In vivo therapy offers:

  • Cost reduction
  • Scalability for rural/semi-urban India
  • Less dependency on advanced infrastructure

Conclusion

This in vivo CAR T-cell breakthrough could democratize access to life-saving immunotherapy, particularly in LMICs like India, by eliminating key bottlenecks of traditional methods. If validated through human trials, it could redefine the future of precision medicine.

UPSC Relevance : 
GS Paper 3 – Science & Tech | Health | Biotechnology

Possible Mains Question : 
Q: What are CAR T-cell therapies? Discuss how innovations in in vivo genetic editing can transform healthcare delivery in India.

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