CART-33 / University of Pennsylvania, Novartis - LARVOL DELTA

EZH1/2 Inhibition Improves the Anti-Tumor Efficacy of CAR and TCR T-Cell Based Therapies Against Multiple Liquid and Solid Tumors (ASH 2024) - "We observed that CART22 and CART79b co-cultured with tazemetostat showed enhanced cytotoxicity (72 hs, CART22-taz vs -DMSO p<0.001; CART79b-taz vs -DMSO p<0.01)...Pretreating an array of MM (e.g. RPMI-8226) and AML (e.g. THP-1, KG-1) cell lines with tazemetostat before exposure to anti-BCMA (CARTBCMA) or anti-CD33 CART (CART33) significantly increased killing efficacy at multiple E : T ratio and even with ineffective single-agent CART doses (72 hs; CARTBCMA-taz vs -DMSO p<0.01; CART33-taz vs -DMSO p<0.001)...Furthermore, we show that the novel EZH2/1 inhibitor valemetostat lead to an increased improvement of tumor killing as compared to EZH2i alone. Mechanistically, we demonstrate that EZH1/EZH2 modulation can unlock the full potential of adoptive T-cell immunotherapy."

Clinical • IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Ewing Sarcoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Adenocarcinoma • Prostate Cancer • Sarcoma • Solid Tumor • CD79B • EZH2 • HER-2

CD33KO-HSPC Infusion Followed by CART-33 Infusion(s) for Refractory/Relapsed AML (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: University of Pennsylvania | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

CD33KO-HSPC Infusion Followed by CART-33 Infusion(s) for Refractory/Relapsed AML (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: University of Pennsylvania

Combination therapy • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

G-CSF Mobilized Apheresis As an Alternative Source of CAR T-Cells (ASH 2022) - "Methods Untransduced T-cells (UTD) and CAR T-cells targeting CD33 (CART33) were manufactured using paired steady state (ss) cells and cells collected after rhG-CSF treatment (mob)...Successful completion of this work may support the use of cryopreserved G-CSF stimulated apheresis units for cell therapy applications. This may allow for an adjunct cell therapy to hematopoietic stem-cell transplant to be manufactured from the same mobilized collection, or provide a means by which previously cryopreserved mobilized units may be utilised, noting frequently lower cumulative chemotherapy exposure in historically cryopreserved T-cells."

CAR T-Cell Therapy • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD33 • CD34 • CD8 • CSF3 • IL15 • IL7

Engineering Resistance to Antigen-Specific Immunotherapy in Normal Hematopoietic Stem Cells By Gene Editing to Enable Targeting of Acute Myeloid Leukemia (ASH 2016) - "Gene editing to remove CD33 from normal HSPCs allows persistent myelopoiesis during CART33-mediated eradication of AML, thus paving the way to a novel system that maximizes efficacy while minimizing toxicity. We envision future clinical translation of this approach by administering CD33 KO HSPCs as an allogeneic stem cell transplant in combination with CART33 in patients with AML."

Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology