Possible UPSC Questions
Prelims (Objective)
- The June 2025 Science study on CAR-T therapy used which delivery vehicle to insert mRNA directly into circulating T-cells?
A) Viral vectors B) Electroporation C) Lipid nanoparticles D) CRISPR plasmids - CAR-T therapy most commonly targets which surface antigen in B-cell malignancies?
A) CD4 B) CD19 C) PD-L1 D) EGFR
Mains (150 words)
“Conventional CAR-T therapy is limited by cost, infrastructure and safety. Explain how the new in-vivo mRNA–LNP approach addresses these drawbacks and assess its relevance for India’s cancer burden.”
Quick Outline of Key Facts
- Conventional CAR-T: Ex-vivo gene-engineering of patient’s T-cells; uses viral vectors, lymphodepleting chemotherapy; ₹60–70 lakh in India.
- New platform (Science, 19 June 2025):
- CD8-targeted lipid nanoparticles (tLNPs) ferry mRNA encoding CAR directly into circulating CD8+ T-cells.
- Tested in mice (CD19 CAR) and cynomolgus monkeys (CD20 CAR); achieved 85-95 % conversion of CD8+ lineage, broad B-cell depletion, tumour regression.
- Uses Lipid 829 – fast-clearing, low-inflammation carrier.
- Works without viral vectors, bespoke cell factories or lymphodepleting chemo; dosing resembles biologic infusion (2-3 IV doses, 72 h apart).
- One monkey developed severe immune hyper-reaction, underscoring need for cautious human trials.
- Broader promise: Temporary CAR expression may “reset” immune system in autoimmune diseases (lupus, myositis).
- Indian context: High prevalence of B-cell cancers (DLBCL 34-60 % of NHL; ALL 75 % of childhood cancers) and rising autoimmune disorders; limited cell-therapy units. Infusion-based model could cut costs and expand access if future trials succeed.
Summary
Chimeric antigen-receptor (CAR) T-cell therapy, which genetically re-arms a patient’s own T-lymphocytes to hunt cancer cells, has revolutionised outcomes in refractory leukaemia and lymphoma. Yet its use is constrained by personalised cell harvesting, sophisticated viral engineering, lymphodepleting chemotherapy and steep prices (₹60-70 lakh in India). A multinational team (NIH-Capstan-UPenn) has now reported an in-vivo alternative that shifts the entire engineering process inside the body.
Their platform packages messenger-RNA instructions for a tumour-seeking CAR inside lipid nanoparticles (LNPs)—the same carrier class popularised by mRNA vaccines. By attaching an antibody “address label” against CD8, the LNPs hone specifically to cytotoxic T-cells. In mouse models, CD8-tLNPs encoding a CD19-CAR reprogrammed circulating T-cells within days and eradicated B-cell tumours; in cynomolgus monkeys, a CD20-CAR version wiped out 95 % of B-cells across blood, spleen and marrow after just two or three infusions.
Because the mRNA does not integrate into the genome, CAR expression is transient, lowering risks of insertional mutagenesis. The protocol also bypassed lymphodepleting chemotherapy—reducing infection risk—and required only standard IV dosing, more akin to giving a biologic drug than executing a bespoke cell-manufacturing workflow. A new biodegradable Lipid 829 carrier showed minimal liver toxicity and muted cytokine release, although one monkey succumbed to an extreme immune flare, highlighting the need for meticulous dose-finding in human trials.
Beyond oncology, the researchers demonstrated ex-vivo that patient-derived lupus and myositis blood samples could be similarly purged of auto-reactive B-cells, hinting at a future role in autoimmune “immune-reset” therapy.
For India—where aggressive B-cell lymphomas dominate non-Hodgkin cases and acute lymphoblastic leukaemia tops childhood cancers—an off-the-shelf, infusion-based CAR modality could slash costs, circumvent scarce GMP cell-labs and expand reach to tier-2 cities. It dovetails with the government’s push for indigenous biologics under schemes such as PLI-pharma and Make-in-India. Nonetheless, scalability, reproducibility and long-term safety must clear stringent clinical and regulatory hurdles before adoption.
Significance to the UPSC Exam
- GS III – Science & Tech: Illustrates cutting-edge gene-therapy convergence (mRNA, LNP, immuno-oncology) and its translation challenges.
- GS II – Health: Connects tech innovation to accessibility, health-equity and Ayushman Bharat cost containment.
- Essay & Interview: Provides contemporary case study on disruptive biomedical innovation, indigenous manufacturing potential and ethical-regulatory balancing in healthcare.
