What is CAR T-cell therapy?
- A form of immunotherapy where T-cells are genetically modified to detect and destroy cancer cells.
- Conventional method: T-cells are extracted, engineered with CAR (chimeric antigen receptor) in labs, and re-infused.
- Target cancers: Mostly B-cell driven cancers like leukaemia and lymphoma.
Relevance : GS 3(Science and Technology)
Current Challenges in CAR T-cell Therapy
- Complex & expensive: ₹60–70 lakh per patient in India.
- Requires:
- Personalised lab-based engineering
- Viral vectors for gene delivery
- Chemotherapy for immune suppression
- Risk of severe side effects: cytokine storms, secondary infections, and genetic complications.
New Breakthrough: In Vivo CAR T-cell Engineering
- Published in Science (June 2025): Researchers used mRNA + lipid nanoparticles (LNPs) to deliver CAR instructions inside the body.
- Target: CD8+ T-cells using antibody-tagged LNPs.
- No need for:
- Cell extraction
- Lab processing
- Chemotherapy
Key Preclinical Results
- In mice: Tumours regressed after in vivo reprogramming.
- In monkeys:
- B cells depleted in multiple organs
- 85–95% T-cell reprogramming achieved after 2–3 infusions
- Some immune reset observed in autoimmune models.
Advantages of In Vivo Approach
- Temporary modification via mRNA reduces long-term genetic risks.
- No chemotherapy required → safer for elderly/comorbid patients.
- Potential for mass production and standardised dosing, like vaccines or biologic drugs.
- Uses Lipid 829: a biodegradable carrier with lower inflammation risk.
Safety Considerations
- Mild inflammation seen; manageable with premedication.
- One monkey developed severe immune reaction (HLH) → underlines need for careful dosing.
- Human trials essential to verify safety, reproducibility, and long-term effects.
Relevance for India
- High burden of B-cell cancers (e.g., DLBCL, ALL).
- Rising autoimmune cases post-COVID.
- Existing barriers: Few specialised centres, high costs, limited trained personnel.
- This new infusion-based method could democratise access to CAR T therapy in low-resource settings.
Broader Implications
- Could transform oncology and autoimmune treatment models.
- May set precedent for in vivo gene therapy platforms.
- Offers a path to affordable personalised medicine in developing countries.
