CD6-ADC / Cleveland Clinic - LARVOL DELTA

Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study. (PubMed, Clin Lymphoma Myeloma Leuk) - "To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies."

Journal • CNS Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

A CD6-Targeted Antibody Conjugate (CD6-ADC) Selectively Ablates Alloreactive Proliferating T Cells in Humans and Non-Human Primates (NHPs) (ATC 2024) - "Both the first generation CD6-ADC (4nM) and belatacept (100ug/mL) induced significantly more inhibition than the negative control mAb in RMs (CD4 mean 35.2% and 53.9%; CD8 48.93% and 68.5%) further highlighting the killing by MMAE.* Targeted killing of proliferating alloreactive T cells following transplantation remains an unmet goal in the field. Targeted killing of proliferating alloreactive T cells following transplantation remains an unmet goal in the field. CD6-ADC offers the potential advantages of decreased systemic immunosuppression, drug conservation, and avoidance of off-target effects. Here we have demonstrated the dose-dependent ablation of proliferating alloreactive T cells in both humans and RMs by the CD6-ADC."

Transplantation • CCR7 • CD8 • IFNG • TNFA

A CD6-targeted antibody-drug conjugate as a potential therapy for T cell-mediated disorders. (PubMed, JCI Insight) - "Furthermore, in vivo, whereas the CD6-ADC had no significant detrimental effect on normal T cells in naïve CD6 humanized mice, the same dose of CD6-ADC, but not the controls, efficiently treated two pre-clinical models of autoimmune uveitis and a model of graft-versus-host disease. These results provide evidence suggesting that CD6-ADC could be further developed as a novel therapeutic agent for the selective elimination of pathogenic T cells and treatment of many T cell-mediated disorders."

Journal • Graft versus Host Disease • Immunology • Ocular Inflammation • Ophthalmology • Uveitis

CD6-targeted antibody-drug conjugate as a new therapeutic agent for T cell lymphoma. (PubMed, Leukemia) - "More importantly, systemic or local administration of the CD6-ADC or its humanized version, but not the controls, significantly shrank established tumors in the preclinical mouse model of TCL. These results suggest that CD6 is a novel therapeutic target in TCLs and provide a strong rationale for the further development of CD6-ADC as a promising therapy for patients with these potentially fatal lymphoid neoplasms."

Journal • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

A CD6-Targeted Antibody-Drug Conjugate As a Potential Therapy for T Cell-Mediated Disorders (ASH 2021) - "These data indicate that this CD6-ADC holds promise as a new drug for treating diseases in which T cells are integrally involved in the pathogeneses such as GVHD."

Graft versus Host Disease • Immunology • Inflammation • Ocular Inflammation • Oncology • Ophthalmology • Uveitis

A Novel Aggressive NK Cell Leukemia Cell Line and Mouse Model for Evaluation of Therapeutic Candidates (ASH 2021) - "Single agent of venetoclax, BCL-xl inhibitor (A-1331852), and CDK9 inhibitor (A-1592668), at range of 1 – 1000 nM, had no detectable (BCL-2), mild (BCL-xL), and strong (CDK9) killing activities against CCANKL cells...Administration of either anti-CD6 IgG or CD6-ADC (4 mg/kg) on the same day as inoculation of CCANKL cells in NSG mice blocked engraftment of these malignant cells in NSG mice... A novel aggressive NK cell leukemia cell line and a NSG mouse model were established. The in vitro data support further investigation of the expression features of BCL-2 family proteins in ANKL cases and in vivo evaluation for the efficiency of anti-apoptotic protein inhibitors in this aggressive disease. Further studies targeting CD6 in ANKL is warranted."

IO biomarker • Preclinical • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1 • CD2 • IL2 • MCL1

CD6-Targeted Antibody–Drug Conjugate As a Potential Therapeutic Agent for T Cell Lymphomas (ASH 2021) - "While brentuximab vedotin has shown efficacy in CD30-expressing lymphomas such as anaplastic large cell lymphoma, effective targeted therapies for PTCLs are lacking and this represents an unmet medical need. These results suggest that CD6 is a novel therapeutic target for PTCLs and provide a strong rationale for the further development of CD6-ADC as a promising therapy for patients with this aggressive blood cancer."

CNS Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Leukemia • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Rheumatoid Arthritis • Rheumatology • T Cell Non-Hodgkin Lymphoma • TNFRSF8