Predicting a Response to a Cell-Based Immune Modulating Cancer Therapy

OVERVIEW

Georgetown researchers have designed a novel and innovative prognostic indicator for CAR-T therapy efficacy in patients. The method uses primary tumor biopsies and CAR- T cells in the zebrafish xenograft model to predict which patients will respond to such therapy before the therapy.

BACKGROUND

While chimeric antigen receptor T (CAR-T) cells have emerged as a promising immune therapy for treating multiple types of cancer, over 50% of patients still do not respond to treatment and eventually relapse within six months. Clinicians currently have no way to test the efficacy of CAR-T therapy before prescribing it. Given that the treatment costs about $500,000 a patient and is limited by manufacturing capacity, having a reliable model that can provide prognostic information to clinicians is a game changer in human cancer treatments. CAR-T cell therapy has shown considerable promise for hematologic malignancies. Great efforts are being made to ensure CAR-T cells' high effectiveness in patients with no other treatment option. Testing CAR-T strategies in mice is expensive, laborious, and slow.

Benefit

• Cost-efficient and fast assay
• Overcome limitations of xenogeneic graft-versus-host disease (xeno GVHD)
• High throughput (400 embryos)
• Small tissue requirement (~100 cells)
• Unparalleled in-vivo
  imaging
• Patient-Specific Analysis
• Allows the screening for small compounds, acting synergistically with CAR T cells

Market Application

• A prognostic method to predict patient responsiveness to CAR-T therapy
• Potential use for preclinical evaluation of novel CAR designs containing a small compound-based ON or OFF switch

Publications

• Identifying drivers of breast cancer metastasis in progressively invasive subpopulations of zebrafish-xenografted MDA-MB-231. Molecular biomedicine. 3:16. doi: 10.1186/s43556-022-00080-5.
• Zebrafish Xenografts for Drug Discovery and Personalized Medicine. Trends Cancer. 2020 Jul;6(7):569-579. doi: 10.1016/j.trecan.2020.03.012.
• Cancer Cell Invasion and Metastasis in Zebrafish Models (Danio rerio). doi: 10.1007/978-1-0716-1350-4_1
• https://www.facebook.com/zebrafishthedocumentary/