In Vivo CAR T-cell Therapy – A Potential Breakthrough in Cancer and Autoimmune Disease Care

25 Jun 2025 GS 3 Science & Technology
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What is CAR T-cell Therapy?

  • CAR = Chimeric Antigen Receptor

  • A form of immunotherapy where T-cells are genetically modified to detect and kill specific cancerous cells.

  • Targets: Most commonly CD19 (in B-cell malignancies).

  • Widely used in refractory blood cancers (leukaemia, lymphoma); also being tested in autoimmune diseases like lupus.

               

Traditional CAR T-cell Therapy: Limitations

  • Ex vivo processing:

    • T-cells extracted, engineered in lab using viral vectors, then reinfused.

  • Requires chemotherapy (lymphodepletion) before infusion.

  • High cost in India:

    • ₹60–70 lakh per patient

    • ₹30–35 lakh for CAR cell manufacturing alone.

  • Side effects: Cytokine release syndrome (CRS), infections due to low immunoglobulin, neurological issues.

Breakthrough Study: In Vivo CAR T-cell Engineering 

Key Innovation

  • No lab-based T-cell extraction.

  • Instead, messenger RNA (mRNA) is delivered directly into the body’s CD8+ T-cells via:

    • CD8-targeted Lipid Nanoparticles (CD8-tLNPs) – precise biological targeting.

  • Lipid 829: A biodegradable, liver-friendly nanoparticle for improved safety.

Working Mechanism

  1. CD8-tLNPs carry mRNA coding for CAR (e.g. CD19, CD20).

  2. Delivered via intravenous infusion.

  3. Reprogram CD8+ T-cells inside the body (in vivo).

  4. T-cells begin targeting and killing B-cells, causing tumour regression and B-cell depletion.

  5. CAR expression is temporary – avoids permanent genetic changes.

Experimental Success

  • Mice: Tumours regressed; B-cells depleted.

  • Monkeys (cynomolgus):

    • Up to 85% CD8+ T-cells turned cytotoxic.

    • B-cells eliminated in spleen, bone marrow, lymph nodes.

  • Autoimmune application:

    • B-cells repopulated as naïve, suggesting immune reset.

    • Tested successfully on human blood from lupus, myositis patients (in vitro).

Advantages Over Traditional Method

FeatureTraditional CAR TIn Vivo CAR T (New Study)
Cell extractionRequiredNot required
Viral vectorsYesNo (uses mRNA)
Lymphodepletion (chemo)RequiredNot needed
Cost₹60–70 lakhPotentially much lower
InfrastructureLab-intensiveIV infusion only
PermanenceLong-term risksTemporary gene expression

Safety & Limitations

  • Monkeys tolerated treatment well.

  • Mild inflammation managed with antihistamines, steroids.

  • One monkey developed severe immune overreaction (similar to HLH) – highlights need for dose control and monitoring.

  • No serious liver issues with Lipid 829.

Challenges Ahead

  • Human trials needed to confirm:

    • Long-term safety

    • Efficacy

    • Immune system’s response to repeated doses

  • Concerns about scalability, reproducibility in large-scale production.

Relevance to India

Cancer Burden:

  • B-cell cancers (e.g., DLBCL) = 34–60% of Non-Hodgkin’s Lymphoma

  • Acute Lymphoblastic Leukaemia = Most common paediatric cancer (75%)

India has a high burden of B cell-driven cancers like DLBCL (34–60%) and Acute Lymphoblastic Leukemia (75% of childhood cancers) — both ideal candidates for CAR T-cell therapy.

Autoimmune Surge:

  • 30% rise in autoimmune diseases post-COVID-19.

Systemic Constraints:

  • Limited CAR T infrastructure.

  • Few trained personnel.

  • High costs limit accessibility.

Significance:

  • A simplified infusion-based protocol can:

    • Reach rural and resource-limited settings

    • Drastically reduce costs

    • Increase access to immunotherapy for elderly, comorbid, or frail patients.

This first-of-its-kind in vivo CAR T-cell therapy platform represents a paradigm shift in how immune therapy is delivered. By making the process less personalised, more drug-like, and scalable, it has the potential to democratise advanced cancer and autoimmune treatment globally, including in developing nations like India.



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