CAR T-cell therapy

Byaibio

CAR T-cell therapy is a precision oncology cellular immunotherapy that engineers T cells with chimeric antigen receptors to drive potent, antigen-specific, HLA-independent immune responses against surface antigens. It is best established in hematologic malignancies, but the literature also highlights expanding use in solid tumors such as glioblastoma and osteosarcoma, as well as emerging applications in autoimmune disease and pediatric solid tumors. Recent studies emphasize both efficacy and safety: in relapsed/refractory multiple myeloma, a meta-analysis reported pooled ORR of 91.2% and CR of 75.7%, while long-term follow-up work noted that adverse events were infrequently reported after 3 years post-infusion and that secondary T-cell malignancy was reported mainly within the first 2 years. Mechanistically, advances include metabolic engineering via glut3, inhibition of cathepsin b-mediated trogocytosis, and strategies to reduce exhaustion and improve persistence, infiltration, and antigen-escape control. Delivery and manufacturing are also evolving, with in vivo transgene transfer approaches using lentiviruses, γ-retroviruses, adeno-associated viruses, polymer-based carriers, and viral-like particles. Overall, CAR T-cell therapy remains a transformative ACT platform, but toxicities, rare post-therapy lymphoproliferative disorders, and relapse biology continue to shape optimization efforts.

Hematologic malignancies

  • CAR T-cell therapy showed high efficacy in relapsed/refractory multiple myeloma, with pooled ORR of 91.2% and CR of 75.7% across four trials in patients with POD24. (PMID:41587420)
  • A systematic review and meta-analysis in relapsed/refractory multiple myeloma characterized both efficacy and safety outcomes for CAR-T therapy. (PMID:41508418)
  • In B-cell acute lymphoblastic leukemia, lack of response to prior blinatumomab correlated with significantly worse outcomes after CAR T-cell therapy. (PMID:41643192)
  • CAR T-cell therapy was compared with thiotepa-ASCT at relapse in secondary CNS large B-cell lymphoma, and 5-year follow-up data were reported for a CD20/19 tandem CAR T-cell phase 1 trial in relapsed/refractory B-NHL. (PMID:41490516) (PMID:41512222)

Solid tumors and pediatric oncology

  • CAR T-cell therapy was evaluated as a promising approach for relapsed, refractory, or metastatic osteosarcoma. (PMID:41627173)
  • In preclinical glioblastoma models, on-demand glut3 expression augmented CAR T-cell metabolic fitness and antitumor efficacy. (PMID:41984929)
  • Pediatric solid tumor work described CAR-based adoptive cell therapy as clinically feasible against multiple targets, with engineering strategies aimed at improving infiltration, persistence, and antigen escape. (PMID:41984108)
  • CAR T-cell therapy was highlighted as a therapeutic modality within precision oncology and as part of broader cellular immunotherapy advances for cancer diagnostics and therapeutics. (PMID:41983744) (PMID:41490421)

Mechanistic optimization and engineering

  • CAR T-cell function was improved by selective inhibition of cathepsin b-mediated trogocytosis, which augments antitumor activity. (PMID:42020353)
  • Ponatinib increased TSCM cells by reducing exhaustion in CAR T cells, resulting in durable antitumor efficacy. (PMID:41946709)
  • BASIC was used to engineer CAR T cells with efficient knock-in of large DNA in primary human T cells. (PMID:41485050)
  • A novel nanobody-based TCR-like CAR-T platform targeting PRAME was developed for acute myeloid leukemia, reflecting ongoing target iteration and microenvironment-focused engineering. (PMID:41985065) (PMID:41800605)

Safety, long-term follow-up, and rare complications

  • Long-term follow-up analysis found adverse events were infrequently reported after 3 years post-infusion, while secondary T-cell malignancy was predominantly reported within the first 2 years. (PMID:41974583)
  • CAR T-cell therapy has been associated with rare post-therapy lymphoproliferative and lymphomatous disorders, prompting focused diagnostic review. (PMID:41986503)
  • Secondary T-cell malignancy is described as the adverse event of primary concern based on the mechanism of action of CAR T-cell therapy. (PMID:41986503)
  • A streamlined follow-up process was proposed to automate transfer of focused safety data from electronic health records into a third-party database for CAR T-cell therapy surveillance. (PMID:41974583)

Delivery and in vivo CAR transgene transfer

  • Lentiviruses were discussed as a viral vector strategy for in vivo CAR transgene transfer. (PMID:41490421)
  • γ-retroviruses were also discussed as a viral vector strategy for in vivo CAR transgene transfer. (PMID:41490421)
  • Adeno-associated viruses, polymer-based carriers, and viral-like particles were presented as additional delivery strategies for in vivo CAR transgene transfer. (PMID:41490421)
  • CAR T-cell engineering was framed as a major ACT platform with notable clinical success but limited by toxicities, motivating improved delivery and monitoring approaches. (PMID:41748028)