CD19.CAR-T / Nagoya University Graduate School of Medicine - LARVOL DELTA

CD19 CHIMERIC ANTIGEN RECEPTOR T CELLS GENERATED USING A PIGGYBAC TRANSPOSON VECTOR FOR ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE I STUDY (EBMT 2026) - "All patients underwent lymphodepletion (fludarabine [25 mg/m²/day] and cyclophosphamide [250 mg/m²/day] for 3 consecutive days), followed by a single infusion of the CAR-T cell product. In this first-in-human trial, piggyBac transposon-engineered CD19 CAR-T therapy demonstrated an excellent safety profile, with no DLTs or severe adverse events. The therapy achieved high remission rates and durable disease control, even in individuals with isolated extramedullary relapse. Collectively, these findings support the safety, biological robustness, and long-term efficacy of this nonviral CAR-T platform, highlighting its potential as a scalable, low-cost alternative suitable for broader clinical implementation."

CAR T-Cell Therapy • First-in-human • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Gene Therapies • Graft versus Host Disease • Immunology • CD19

Identification of genes regulating human CAR-T cell proliferation by genome-wide CRISPR screening (PubMed, Rinsho Ketsueki) - "The JAK-STAT pathway was upregulated in CUL5KO CAR-T cells, and CUL5 was associated with the degradation of JAK3 upon activation through IL-2 signaling. CUL5KO CD19 CAR-T cells efficiently suppressed in vivo tumor progression as compared to control CD19 CAR-T cells."

Journal • Oncology • Targeted Protein Degradation • IL2 • JAK3

Cullin-5 deficiency promotes chimeric antigen receptor T cell effector functions potentially via the modulation of JAK/STAT signaling pathway. (PubMed, Nat Commun) - "In vivo, shRNA-mediated knockdown of CUL5 enhances CD19 CAR T treatment outcomes in tumor-bearing mice. Our findings thus imply that targeting CUL5 in the ubiquitin system may enhance CAR T cell effector functions to enhance immunotherapy efficacy."

CAR T-Cell Therapy • Journal • Oncology • Targeted Protein Degradation • JAK1 • JAK3 • STAT3 • STAT5 • UBR5

Protocol to measure human IL-6 secretion from CAR T cell-primed macrophage and monocyte lineage cells in vitro and in vivo using humanized mice. (PubMed, STAR Protoc) - "Here, we describe a protocol to generate anti-CD19 CAR T cells and quantify human monocyte-derived IL-6 cocultured with CAR T cells and target tumor cells in vitro. We further describe a protocol to generate a humanized mouse model and evaluate CAR T cell-associated plasma IL-6 levels in vivo. For complete details on the use and execution of this protocol, please refer to Yoshikawa et al.1."

CAR T-Cell Therapy • Journal • Preclinical • Oncology • IL6

Challenges and prospects for CAR-T therapy (PubMed, Rinsho Ketsueki) - "The number of cases of chimeric antigen receptor T (CAR-T) cell therapy has been rapidly increasing in Japan since Tisagenlecleucel was approved in March 2019, and clinical experience with CAR-T therapy for CD19 has demonstrated that the therapy can be performed safely than initially expected. The current challenge for CAR-T therapy is insufficient response, as about 50% of patients who receive CD19 CAR-T therapy eventually relapse or become refractory...Additionally, the development of novel CAR-T therapies is also desired. In this article, we discuss the current status and future prospects of these issues, including our own efforts."

Journal • Oncology

CD19-CAR-T cell therapy for acute lymphoblastic leukemia (JSH 2023) - No abstract available

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Consolidative allogeneic stem cell transplantation after CD19 CAR-T therapy for ALL (JSTCT 2023) - No abstract available

Bone Marrow Transplantation • Transplantation • CD19

Workshop3 [Propriety of HSCT after CD19 CAR-T therapy (JSTCT 2023) - No abstract available

Bone Marrow Transplantation • CD19

Oral Session 26: CD19 CAR-T: Clinical Outcome I (JSTCT 2023) - No abstract available

Clinical • Clinical data • CD19

Novel xeno-free and serum-free culturing condition to improve piggyBac transposon-based CD19 chimeric antigen receptor T-cell production and characteristics. (PubMed, Cytotherapy) - "Our study supports the usage of xeno-free serum replacement as an alternative source of serum supplements for piggyBac-based CAR T-cell expansion."

CAR T-Cell Therapy • Journal • Hematological Disorders • Hematological Malignancies • Oncology • CD19

Co-Stimulation of CD28/CD40 Signaling Molecule Potentiates CD19CAR-T Cell Functions and Stemness (ASH 2022) - "We then investigated the ability of CD19 CAR T-cell proliferation by coculturing with gamma-irradiated CD19-expressing K562 cells... The CD28/CD40 costimulatory molecule potentiates NF-κB signaling and memory signatures enhancing CD19CAR-T cell proliferation and persistence which translates into greater anti-tumor efficacy in both in vitro and xenograft models. The simplified structural modification of dual T-/B-cell signaling molecule could be advantageous to maximize the CAR-T cell functions and stemness."

CAR T-Cell Therapy • Hematological Malignancies • Immune Modulation • Inflammation • Oncology • CD40 • IFNG • IL2 • TCF7 • TNFA

A Phase I Study of CD19 Chimeric Antigen Receptor-T Cells Generated By the PiggyBac Transposon Vector for Acute Lymphoblastic Leukemia (ASH 2021) - "All patients receive 25mg/m 2 /d of fludarabine and 250mg/m 2 /d of cyclophosphamide for 3 days followed by a single infusion of CAR-T cells. CD19.CAR-T cell infusion produced by the piggyBac transposon gene engineering system was safe in cohort 1 of our study. As no patients had DLT in cohort 1, we are enrolling the patients in further cohorts."

CAR T-Cell Therapy • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Gene Therapies • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Pain • Transplantation • CCR7 • CD19 • CD28 • CD8 • PCR