Work

Exploring Approaches to Enhance the Anti-Leukemic Function of Double Negative T Cell Therapy

Year: 2018

Type: dissertation

Abstract: Chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that contributes to disease relapse and patient death; hence, novel therapies are needed to improve patient outcomes. Our lab has shown that allogeneic double negative T cells (DNTs) target the majority, but not the entirety, of primary AML blasts in vitro and in patient-derived xenograft models. Given the differences in the modes of action of DNTs and chemotherapy, we sought to determine if DNT therapy can be combined with conventional chemotherapy to target chemotherapy-resistant disease. To this end, we employed a xenograft model and in vitro assays. To further understand AML resistance or susceptibility to DNTs, we conducted a CRISPR screen to discover genes that may influence DNT-mediated cytotoxicity of AML. Overall, our results demonstrate the enhanced efficacy of DNT therapy following conventional chemotherapy and also shed light on mechanisms involved in the interactions between DNTs and AML.

Source: TSpace (University of Toronto)

Author: Branson Chen

Language: English

Topic: Acute Myeloid Leukemia Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Government of Ontario, University of Toronto, Canadian Institutes of Health Research, Toronto General Hospital Research Institute, University Health Network

OpenAlex ID: W3159213865

Cites: 200

Cited by:

Related to: 10