HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma
Abstract
Abstract CD30-directed chimeric antigen receptor T-cell therapy (CART30) has limited efficacy in relapsed or refractory patients with CD30+ lymphoma, with a low proportion of durable responses. We have developed an academic CART30 cell product (HSP-CAR30) by combining strategies to improve performance. HSP-CAR30 targets a proximal epitope within the nonsoluble part of CD30, and the manufacturing process includes a modulation of ex vivo T-cell activation, as well as the addition of interleukin-21 (IL-21) to IL-7 and IL-15 to promote stemness of T cells. We translated HSP-CAR30 to a phase 1 clinical trial of 10 patients with relapsed/refractory classic Hodgkin lymphoma (HL) or CD30+ T-cell non-Hodgkin lymphoma. HSP-CAR30 was mainly composed of memory stem–like (TSCM-like) and central memory (TCM) CAR30+ T cells (87.5% ± 5%). No dose-limiting toxicities were detected. Six patients had grade 1 cytokine release syndrome, and no patient developed neurotoxicity. The overall response rate was 100%, and 5 of 8 patients with HL achieved complete remission (CR). An additional patient with HL achieved CR after a second HSP-CAR30 infusion. Remarkably, 60% of patients have ongoing CR after a mean follow-up of 34 months. CAR30+ T cells at expansion peak had a predominance of TSCM and TCM cells, and CAR30+ T cells remained detectable in 3 of 5 evaluable patients at least 12 months after infusion. Our study shows that selection of the epitope targeting CD30 and ex vivo preservation of less-differentiated memory T cells may enhance the efficacy of CART30 in patients with refractory HL. This trial is registered at www.clinicaltrials.gov (NCT04653649).
Article Details
Authors (19)
Ana Carolina Caballero
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Cristina Ujaldón-Miró
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Paula Pujol-Fernández
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Rosanna Montserrat-Torres
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Maria Guardiola-Perello
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Eva Escudero-López
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Irene Garcia-Cadenas
Hematology Department. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Albert Esquirol
9Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Rodrigo Martino
4Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Paola Jara-Bustamante
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Pol Ezquerra
4Unit of Genomics of Complex Disease, Research Institute of Sant Pau Hospital, Barcelona, Spain
José Manuel Soria
Eva Iranzo
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Maria-Estela Moreno-Martinez
6Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain
Mireia Riba
6Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain
Jorge Sierra
9Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau and José Carreras Leukemia Research Institutes, Barcelona, Spain
Carmen Alvarez-Fernández
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Laura Escribà-Garcia
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Javier Briones
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain