CAR-T cells / Chinese PLA General Hospital - LARVOL DELTA

Efficacy and safety profile of inaticabtagene autoleucel in Chinese patients with Philadelphia chromosome-positive b-ALL: Insights from real-world data (ASH 2025) - P | "Prior therapies included hematopoietic stem cell transplantation (HSCT) (24.1%), inotuzumab ozogamicin (14.8%), and blinatumomab (24.1%)...The median infusion dose was 0.60 (range: 0.44–1.00) × 10 8 viable CAR-T cells, with 88.9% of patients receiving bridge therapy...All patients recovered without sequelae: 9 received corticosteroids, and 11 received tocilizumab. Conclusion Real-world data demonstrate that Inati-cel exhibits excellent efficacy in patients with Ph+ B-ALL, yielding low toxicity, short treatment cycles, high complete molecular response rates, and favorable long-term survival. Extended follow-up could illuminate the long-term outcomes of Inati-cel use."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Central Nervous System Leukemia • Hematological Malignancies • Leukemia • ABL1 • IKZF1

Efficacy and safety profile of inaticabtagene autoleucel in Chinese adult patients with B-cell acute lymphoblastic leukemia who relapsed after their transplant: Insights from real-world data (ASH 2025) - P | "The median infusion dose was 0.60 (range: 0.42–1.00) × 10 8 viable CAR-T cells...Patients with and without prior blinatumomab exposure had similar OS (p = 0.62) and RFS (p = 0.58); the same was true for prior inotuzumab ozogamicin exposure (p = 0.86 and p = 0.67, respectively)...Conclusion Real-world data demonstrate that Inati-cel exhibits excellent efficacy in patients with B-ALL who relapse after HSCT and in patients with active extramedullary disease; its safety was also established. Extended follow-up is warranted to fully characterize the long-term outcomes of Inati-cel use."

Clinical • IO biomarker • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Central Nervous System Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Transplantation • IKZF1 • TP53

Novel bispecific epitope anti-CD5 nanobody CAR-T cells for refractory or relapsed T-cell malignancies (ASH 2025) - P1/2 | "We optimized the novel bispecific epitope anti-CD5 nanobody CAR construct, and showssuperior cytotoxic activity comparing with CD5 CAR (IASO Biotech) in vitro. We also got preliminary safetyand efficacy profiles in r/r T-cell lymphoma. This clinical trial is still ongoing, and long-term efficacy andclinical complication of CD5 CAR-T cell therapy still require further investigation."

CAR T-Cell Therapy • IO biomarker • Cutaneous T-cell Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • TERC

Enhanced efficacy and safety of optimized tandem CD19/CD20 CAR T-cell Therapy in refractory/relapsed B-cell lymphoma (ASH 2025) - P1 | "While tandem CD19/CD20 CAR-T cells show promise, we observed limitations in thefunctionality and persistence of a second-generation construct (CAR2019)...Common grade ≥3 adverseevents within 1 month were neutropenia (100%), thrombocytopenia (62%), and infection (25%).CAR2019(AS) exhibited robust expansion (median peak: 48486.9 copies/μg gDNA on day 10).ConclusionsOur novel incorporation of protease cleavage sites (AS) significantly enhances tandem CD19/CD20 CAR-Tfunctionality and exhaustion resistance. CAR2019(AS) achieves exceptional clinical efficacy with promisingsurvival in r/r BCL, establishing a potent dual-targeting strategy to overcome CD19 monotherapylimitations."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • CD20

Safety and preliminary efficacy of a novel loop-optimized, BCMA/CD19 bispecific CAR-T therapy for refractory or relapsed autoimmune diseases patients (ASH 2025) - P1/2 | "Their persistent killing capacity against CD19+ or BCMA+ targets was comparable to that of singleCD19 or BCMA CAR-T cells. Novel Loop dual CD19/BCMA CAR-T demonstrated favorable efficacy and safety inrelapsed/refractory autoimmune diseases and new clinical trial is ongoing (NCT06947460)."

Clinical • IO biomarker • Cardiovascular • Fibrosis • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Lupus • Lupus Nephritis • Nephrology • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Rheumatology • Scleroderma • Sjogren's Syndrome • Systemic Lupus Erythematosus • Systemic Sclerosis

Intrinsic NPRL2 and NPRL3 regulate the sensitivity of B-cell malignancies to CAR-T cell therapy. (PubMed, J Genet Genomics) - P1/2 | "Mechanistically, NPRL2/NPRL3 suppresses mTORC1 activity within tumor cells, negatively regulating the conjugation between tumor cells and CAR-T cells, consequently impairing CAR-T cell activation and cytotoxic function, ultimately facilitating immune escape. As therapeutic strategies, either genetic ablation of tumor-intrinsic NPRL2/NPRL3 or pharmacological activation of mTORC1 enhances CAR-T cell activation, cytotoxic degranulation, and tumor clearance both in vitro and in vivo. In conclusion, targeting tumor NPRL2/NPRL3 or directly activating mTOR represents a promising combinational strategy to potentiate CAR-T efficacy and overcome resistance in clinical practice."

IO biomarker • Journal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Functional Diversification and Dynamics of CAR-T Cells in B-ALL Patients (ASH 2023) - "Correspondence to Drs. Zongcheng Li, Bing Liu, Lilin Ye, Yu Lan and Liang Huang."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • GZMB • GZMH • GZMK • VPREB1

Changes in Glycosylation on the Cell Surface Result in Highly Potent and Long-Lasting Allogeneic CAR-T Therapy in Patients (ASH 2024) - "Thereby, it not only combats host rejection but also improves the potency of allo-CAR T cells...Following lymphodepletion of fludarabine (30-50 mg/m2/d) and cyclophosphamide (500-1000 mg/m2/d) for a duration of 3 days, patients receive a single-dose infusion of ET-901 at escalating doses of 1*10e6/kg, 3*10e6/kg, and 10*10e6/kg...All patients demonstrated objective responses, with significant CAR-T cell expansion, confirming the engineered cells' long-term immune privilege and activity. This represents a significant step in making allogeneic CAR T-cell therapy more viable and effective."

Clinical • Anemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Thrombocytopenia • B2M

Preclinical development and a case report of a nanobody-based CLDN18.2 CAR-T IMC002 with reduced on-target off-tumor toxicity. (PubMed, Mol Cancer Ther) - "The highest non-severely toxic dose was 5×108 CAR-T cells/kg. In the clinical case report, we present a case with unresectable advanced gastric cancer achieved pathological complete response 10 months after IMC002 infusion and no signs of recurrence were indicated in subsequent clinical and radiological follow-ups. IMC002 shows effectiveness and safety in CLDN18.2-positive gastric and pancreatic cancer and its favorable profiles support further clinical development."

Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

BC19IGG4: Exploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease (clinicaltrials.gov) - P2 | N=9 | Not yet recruiting | Sponsor: Chinese PLA General Hospital

IO biomarker • New P2 trial • Immunology • Inflammation

BC19IGG4: Exploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease (clinicaltrials.gov) - P2 | N=9 | Recruiting | Sponsor: Chinese PLA General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Immunology • Inflammation

Glycan shielding enables TCR-sufficient allogeneic CAR-T therapy. (PubMed, Cell) - P1/2 | "In a phase I clinical trial, SPPL3-null, T cell receptor (TCR)-deficient anti-CD19 allogeneic CAR-T cells reached the safety primary endpoint, with grade 3 or higher cytokine release syndrome (CRS) observed in 3 out of 9 patients with relapsed/refractory B cell non-Hodgkin lymphoma (B-NHL) (ClinicalTrials.gov: NCT06014073). We therefore evaluated the safety of SPPL3-null, TCR-sufficient CAR-T therapy on three patients with lymphoma or leukemia for compassionate care and observed no clinical signs of graft-versus-host disease. Our findings suggest glycan shielding by SPPL3 deletion is a promising direction for optimizing universal CAR-T therapies."

Journal • B Cell Non-Hodgkin Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CAR19BCMA CAR-T Cells for the Treatment of R/R Plasma Cell Neoplasms (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Chinese PLA General Hospital

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Disruption of cell-intrinsic PCSK9 enhances the antitumor efficacy of CD8+ T cells. (PubMed, J Immunother Cancer) - "These findings indicate that PCSK9 inhibits the antitumor function of CD8+ T cells, suggesting it may be a promising target for enhancing T-cell-based cancer immunotherapy."

IO biomarker • Journal • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • PCSK9