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Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study.
- Source :
-
Cell research [Cell Res] 2022 Nov; Vol. 32 (11), pp. 995-1007. Date of Electronic Publication: 2022 Sep 23. - Publication Year :
- 2022
-
Abstract
- Chimeric antigen receptor (CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts. Allogeneic CAR-T cells, generated from healthy donor T cells, can provide ready-to-use, blast-free therapeutic products, but their application could be complicated by graft-versus-host disease (GvHD) and host rejection. Here we developed healthy donor-derived, CD7-targeting CAR-T cells (RD13-01) with genetic modifications to resist fratricide, GvHD and allogeneic rejection, as well as to potentiate antitumor function. A phase I clinical trial (NCT04538599) was conducted with twelve patients recruited (eleven with T cell leukemia/lymphoma, and one with CD7-expressing acute myeloid leukemia). All patients achieved pre-set end points and eleven proceeded to efficacy evaluation. No dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade ≥ 3) were observed. 28 days post infusion, 81.8% of patients (9/11) showed objective responses and the complete response rate was 63.6% (7/11, including the patient with AML). 3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation. With a median follow-up of 10.5 months, 4 patients remained in complete remission. Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) reactivation was observed in several patients, and one died from EBV-associated diffuse large B-cell lymphoma (DLBCL). Expansion of CD7-negative normal T cells was detected post infusion. In summary, we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7 <superscript>+</superscript> hematological malignancies. Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7 <superscript>+</superscript> tumors.<br /> (© 2022. The Author(s) under exclusive licence to Center for Excellence in Molecular Cell Science, CAS.)
- Subjects :
- Humans
Herpesvirus 4, Human
Graft vs Host Disease etiology
Receptors, Chimeric Antigen genetics
Epstein-Barr Virus Infections complications
Hematopoietic Stem Cell Transplantation adverse effects
Hematopoietic Stem Cell Transplantation methods
Hematologic Neoplasms therapy
Hematologic Neoplasms complications
Leukemia, Myeloid, Acute pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1748-7838
- Volume :
- 32
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell research
- Publication Type :
- Academic Journal
- Accession number :
- 36151216
- Full Text :
- https://doi.org/10.1038/s41422-022-00721-y