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

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