Year: 2016
Type: dissertation
Abstract: The adoptive transfer of T lymphocytes expressing chimeric antigen receptors (CARs) has become a promising treatment for various cancers. CARs have been shown to redirect the cytotoxicity of T lymphocytes towards cancerous cells independent of the interactions between T cell receptors and major histocompatibility complexes. Given that CARs tie together an extracellular recognition domain with intracellular signaling domains of immune cells, there exists flexibility in designing CARs specific for different antigens in order to target different malignancies. Here, we established murine antibodies specific for CD138 with the goal of designing a novel CAR. We designed a 2nd generation CAR using a single chain variable fragment derived from the 3E9B6 monoclonal antibody as the extracellular recognition domain. The expression of the 3E9B6 HL CAR specifically enhanced the cytotoxicity of the NK-92 cell line against CD138+ cells. Downstream activation of ZAP70 in NK-92 3E9B6 HL CAR cells was also dependent on the presence of CD138+ target cells. This work shows that the 3E9B6 HL CAR is functionally able to recognize CD138 and to initiate the CD3Îś activation pathway.
Source: TSpace (University of Toronto)
Author: Elliot Berinstein
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2886770016