2026-04-17T13:53:56Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/126882025-10-24T10:33:48Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Cwynarski, Kate author Tholouli, Eleni author Menne, Tobias author Irvine, David A. author Balasubramaniam, Nivetha author IACOBONI, GLORIA author 2025-03-04T12:20:52Z 2025-03-04T12:20:52Z 2024 2025-01 CAR T cell therapy; Peripheral T cell lymphoma Teràpia de cèl·lules T; Limfoma perifèric de cèl·lules T Terapia de células T; Linfoma periférico de células T Relapsed/refractory peripheral T cell lymphomas (PTCLs) are aggressive tumors with a poor prognosis. Unlike B cell lymphomas, treatment of PTCL has not benefited from advances in immunotherapy. This is largely due to a lack of suitable target antigens that discriminate malignant from normal T cells, thus avoiding severe immunosuppression consequent to depletion of the entire T cell compartment. We recently described a targeting strategy based on the mutually exclusive expression of T cell antigen receptor beta-chain constant domain (TRBC) 1 and 2. Selective targeting of the T cell antigen receptor beta-chain expressed by the (clonal) malignancy spares normal T cells expressing the other chain. The LibraT1 study is an ongoing, multicenter, international, single-arm phase 1/2 study of TRBC1-directed autologous chimeric antigen receptor (CAR) T cells (AUTO4) in relapsed/refractory TRBC1-positive PTCL. Primary objectives were assessment of safety and tolerability of AUTO4 infusion. Key secondary endpoints included efficacy, CAR T cell expansion and persistence. Here we describe the findings from dose escalation in LibraT1 in the first ten patients, in a non-prespecified interim analysis. AUTO4 resulted in low frequency of severe immunotoxicity, with one of ten patients developing grade 3 cytokine release syndrome. Complete metabolic response was observed in four of ten evaluable patients, with remissions being durable beyond 1 year in two patients. While an absence of circulating CAR T cells was observed, CAR T cells were readily detected in lymph node biopsy samples from sites of original disease suggesting homing to tumor sites. These results support the continuing exploration of TRBC1 targeting in PTCL. ClinicalTrials.gov registration: NCT03590574. This study was funded by Autolus Therapeutics and Innovate UK (grant TS/N010167/1). We are indebted to the patients and their families for their commitment. We thank all the clinical investigators, research nurses and study coordinators. We also acknowledge the contribution of the Independent Data Monitoring Committee members. http://hdl.handle.net/11351/12688 Cèl·lules T Sistema limfàtic - Càncer - Immunoteràpia Limfomes - Immunoteràpia DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, T-Cell::Lymphoma, T-Cell, Peripheral Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células T::linfoma de células T periféricas Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial