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CD3 bispecific for the treatment of ROR2-positive NSCLC

CD3 双特异性用于治疗 ROR2 阳性 NSCLC

基本信息

批准号：
10760580
负责人：
Jean-Loup Romet-Lemonne
金额：
$ 40万
依托单位：
TRAVERSE BIOTECH II INC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10760580
关键词：
Adult Affinity Antibodies Antibody Affinity Antigen Targeting Antitumor Response Binding Biotechnology Bispecific Antibodies CAR T cell therapy CD3 Antigens Cancer Etiology Cancer Patient Cell Death Cell-Mediated Cytolysis Cells Cessation of life Clinical Collaborations Complex Development Disease Dose Embryonic Development Environment Evaluation Family member Future Goals Guidelines Human Immune Immune checkpoint inhibitor Immune system Immunohistochemistry Immunologic Stimulation Immunotherapy In Vitro Industry Standard Invaded Letters Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Mediating Membrane Messenger RNA Modality Modeling Newly Diagnosed Non-Small-Cell Lung Carcinoma Oncology Orphan Patients Phase Prognosis ROR1 gene Receptor Protein-Tyrosine Kinases Receptor Signaling Research Research Personnel Resources Risk Role Sampling Sequence Homology Signal Transduction Site Solid Solid Neoplasm Squamous Cell Lung Carcinoma Survival Rate T-Lymphocyte Therapeutic Therapeutic Effect Tissue Microarray Tissue Sample Tissues Toxic effect Tumor Antigens Tumor Cell Line Tumor Volume Validation WNT Signaling Pathway Woman anti-PD-L1 antibodies antitumor effect arm cancer cell cancer diagnosis cell motility chimeric antigen receptor T cells clinical application cross reactivity design human tissue humanized mouse improved outcome in vivo in vivo Model innovation men mouse model nanomolar neoplastic cell nonhuman primate novel novel therapeutics polarized cell pre-clinical preclinical development receptor reconstitution success targeted treatment therapy development tumor tumor growth tumor microenvironment tumor xenograft validation studies

项目摘要

Project Summary We are developing a novel CD3-bispecific antibody product, TB-Bs1, for the treatment of lung cancer. Lung cancer is the leading cause of cancer deaths in both men and women in the U.S. each year, with non-small cell lung cancer (NSCLC) making up the majority of cases. NSCLC also has one of the lowest survival rates, with 5- year survival for new diagnoses at only 18%. Treatment options remain relatively unchanged over the past decade, despite the emergence of new immunotherapies such as checkpoint inhibitors and CAR-T cell therapy. The success of these modalities is heterogeneous at best, largely due to the complexity of the tumor microenvironment (TME). Specifically, on-target off-tumor toxicity and reduced immune stimulation within the tumor have limited immunotherapy success. Therefore, exploration of new targets and therapeutic modalities that can specifically and potently direct immune-mediated cancer cell death at the tumor site would provide NSCLC patients with a much-needed option. Herein this Phase I application, we are advancing TB-Bs1 through preclinical proof-of-concept in vivo studies in NSCLC. TB-Bs1 is built on the Fc-inert CD3 DuoBodyÒ bispecific antibody platform and has a unique tumor associated antigen (TAA) target, receptor tyrosine kinase orphan receptor 2 (ROR2). ROR2, a Wnt signaling membrane receptor that is expressed and active during embryogenesis but is absent from healthy tissues in adults, is a new target that has yet to be validated. We present here a highly specific anti-ROR2 antibody that is built on a clinically validated bispecific platform. We will first determine ROR2 expression in a panel of NSCLC tumors as well as in normal human tissue samples. Then we will evaluate the anti-tumor therapeutic effect of TB-Bs1 in a proof-of-concept ROR2-positive NSCLC humanized mouse model. These results will support the launch of TB-Bs1 into full-scale preclinical development for the treatment of ROR2-positive NSCLC in a future Phase II application.

项目总结