SMART 102 / Smart Immune, Public Assistance - Paris Hospitals - LARVOL DELTA

GMP-manufactured allogeneic human t lymphoid progenitors (HTLP) promote early and sustained T-cell recovery after CD34+-selected haploidentical HSCT in SCID patients : Final results of the htlp-SCID study (ASH 2025) - P1/2 | "Four SCID patients received HTLP following CD34+-selected HSCT. HTLP products showed robustdifferentiation (median 79.7% CD7+ CD3–) and expansion (median 14.7-fold). Infused doses ranged from0.1 to 0.3 ×10⁶ CD7+CD3- cells/kg, with minimal residual CD3+ cells (<11.2/kg)."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hepatology • Immunology • Infectious Disease • Primary Immunodeficiency • CD34 • CD7 • TRB

Human Pro-T-Cell Manufacturing in Vitro Is a Safe Procedure for Hematopoietic Stem Cell Transplantation with Delayed T-Cell Reconstitution: Interim Results from 2 Different Clinical Trials (ASH 2023) - P1/2 | "The GMP generation of Human T lymphoid Progenitors (HTLP) that are competent to rapidly become in vivo differentiated functional and thymic-educated T-cells may overcome the post-transplant delayed immune reconstitution... First infusions of HTLP in both clinical trials confirmed the safety and reproducible GMP manufacturing. HLTP offers an exciting perspective for improving immune reconstitution in alternative hematopoietic transplants."

Preclinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Primary Immunodeficiency • Transplantation • CD34 • CD7

Ex Vivo Generation of Human T-Cell Progenitors from Cord Blood CD34+ Cells Can Accelerate Immune Reconstitution after Umbilical Cord Blood Transplantation in Adult Patient with Hematologic Malignancies (ASH 2024) - P1/2 | "We developed a protocol using ex vivo- committed Human T Lymphoid Progenitor cells (HTLPs) that seed the thymus immediately after transplantation, accelerating the production of mature and polyclonal T cells.Methods : The safety and efficacy of HTLPs (characterized by CD7 surface marker) to accelerate immune reconstitution were evaluated in a phase I/II multicentric and single-arm clinical trial after a single UCBT in adults with hematologic malignancy, adding back HTLPs generated from a second UCB (NCT04707300)...More interestingly, a 63-year-old patient restored a higher thymic function, suggesting regenerative properties of HTLPs on thymic epithelium.Conclusions : First dosing of HTLPs in the first human clinical trials using UCB confirmed the safety and the reproducibility of GMP manufacturing. Thus, HTLPs may offer an exciting perspective for improving immune reconstitution in HSCT."

Preclinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Oncology • Transplantation • CD31 • CD34 • CD7 • CD8 • PECAM1

Beyond conventional adoptive T cell therapy. (PubMed, J Allergy Clin Immunol) - "Human T lymphoid progenitor (HTLP)-based immunotherapy might be a valuable, complementary approach for increasing the effectiveness of current treatments for T cell deficiencies...After injection in NSG mice, ProTcell can differentiate and be educated in the thymus to generate simple positive T-cells. Here, we summarize the current state of preclinical and clinical research using this approach, highlighting its potential advantages and current limitations for immune reconstitution therapies."

Journal • Review • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Transplantation • CD34 • CD7

Study Evaluating the Safety and the Efficacy of Human T Lymphoid Progenitor (HTLP) Injection to Accelerate Immune Reconstitution After Umbilical Cord Blood (UCB) Transplantation in Adult Patients With Hematologic Malignancies (HTLP-ONCO) (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial completion date: Aug 2027 ➔ Aug 2028 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Oncology • Transplantation • CD34 • CD7 • HLA-DRB1

Feeder-cell-free system for ex vivo production of natural killer cells from cord blood hematopoietic stem and progenitor cells. (PubMed, Front Immunol) - "Cord blood CD34+ HSPCs were cultured in our established hDLL 4 culture system and generated large numbers of human T lymphoid progenitors (ProTcells) in 7 days...Our ex vivo culture process supports scalable ProT-NK cell production in high yields, reducing dependency on feeder cells and mitigating contamination risks. Our findings demonstrate the feasibility of generating large, functional NK cell populations from HSPCs isolated from readily available cord blood sources and offer an efficient alternative to PB-NK cell therapies."

IO biomarker • Journal • Preclinical • Graft versus Host Disease • Immunology • Oncology • CD34 • GZMA • NCAM1 • TNFA

Study Evaluating the Safety and the Efficacy of Human T Lymphoid Progenitor (HTLP) Injection to Accelerate Immune Reconstitution After Umbilical Cord Blood (UCB) Transplantation in Adult Patients with Hematologic Malignancies (HTLP-ONCO) (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial completion date: Feb 2026 ➔ Aug 2027 | Trial primary completion date: May 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Oncology • Transplantation • CD34 • CD4 • CD7 • HLA-DRB1

Smart Immune and Greater Paris University Hospitals (AP-HP) begin groundbreaking Phase I/II trial with ProTcell, a thymus-empowered T-cell therapy platform, in adults with blood cancers (GlobeNewswire) - "Smart Immune SAS...and the Greater Paris University Hospitals (AP-HP), announced today that SMART102, a human T-lymphoid progenitor cell injection derived from cord blood using Smart Immune’s ProTcell™ platform, has entered clinical testing in a trial sponsored and led by Great Paris University Hospitals (AP-HP)....The trial has been designed to assess the potential of the ProTcell™ technology to improve clinical outcomes of HSCT. Overall survival in this patient group is currently low at 5 years post-HSCT, with around 50% mortality....No safety-related issues or dose limiting toxicity have been reported in the first patient enrolled in the trial to date. Preliminary data from the trial are expected in around 18 months."

P1/2 data • Trial status • Hematological Malignancies • Oncology