(1) Quintarelli C (2) Del Bufalo F (3) De Ioris MA (4) Guercio M (5) Algeri M (6) Pagliara D (7) Silvestris DA (8) Di Nardo M (9) Sinibaldi M (10) Di Cecca S (11) Iaffaldano L (12) Manni S (13) Fustaino V (14) Garganese MC (15) Colafati GS (16) Bertaina V (17) Becilli M (18) Mastronuzzi A (19) Fabozzi F (20) Gunetti M (21) Iacovelli S (22) Bugianesi R (23) Macchia S (24) Li Pira G (25) Cefalo MG (26) Leone G (27) Del Baldo G (28) De Angelis B (29) Locatelli F

Nature medicine

Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation. All patients experienced grade 2 or 3 cytokine release syndrome and one grade 2 neurotoxicity. Moderate acute graft-versus-host-disease occurred in four patients. ALLO_GD2-CART01 persisted for >6_weeks. Post-treatment, two complete responses were achieved and one maintained; in addition, one partial response and one stable disease were observed. Comparing the transcriptomic profiles obtained by RNA sequencing analyses of drug products with patient-matched, peripheral blood ALLO_GD2-CART01 collected at expansion, we found upregulation of genes associated with T cell activation and migration. In addition, after infusion, transcriptomic signaling analysis showed enrichment of genes involved in response to decreased oxygen levels, humoral immune response, cell polarization and immune-synapse formation. In comparison to autologous CAR T cells, ALLO_GD2-CAR T cells were characterized by pathways associated with T cell proliferation, immune-synapse formation and cell chemotaxis. The safety and efficacy of ALLO_GD2-CART01 in children with r/r HR-NB deserve further investigation in a prospective trial.

Author Info: (1) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Ita

Author Info: (1) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. (2) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (3) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (4) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (5) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. Department of Health Sciences, Magna Graecia University, Catanzaro, Italy. (6) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (7) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (8) Pediatric Intensive Care Unit, IRCCS, Bambino Ges Children's Hospital, Rome, Italy. (9) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (10) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (11) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (12) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (13) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (14) Nuclear Medicine Unit/Imaging Department, IRCCS, Bambino Ges Children's Hospital, Rome, Italy. (15) Imaging Department, IRCCS, Bambino Ges Children's Hospital, Rome, Italy. (16) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (17) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (18) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (19) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (20) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (21) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (22) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (23) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (24) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (25) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (26) Transfusion Unit, Department of Laboratories, IRCCS, Bambino Ges Children's Hospital, Rome, Italy. (27) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (28) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. (29) Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Ges Children's Hospital, Rome, Italy. franco.locatelli@opbg.net. Catholic University of the Sacred Heart, Department of Life Sciences and Public Health, Rome, Italy. franco.locatelli@opbg.net.

Citation: Nat Med 2025 Jan 15 Epub01/15/2025

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/39815015

Tags: