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CRISPR - Activation and knockout screens to augment anti-tumor T cell responses

Persone

 

Geiger R.

(Responsabile)

Abstract

Immunotherapy is proving to be an effective therapeutic approach to treat cancer. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need to identify additional targets and to develop novel and more effective approaches. In this project, we aim to perform pooled CRISPR-activation and CRISPR-knockout screens in primary human T cells to identify the genes that govern effective T cell responses to tumors. We identified a list of ~3,000 metabolic genes, which will be either deleted or activated in T cells to reveal casual relationships with anti-tumor functionality. In Aim 1, we will perform pooled CRISPR screens to identify genes that affect the effector functions of T cells under metabolically challenging conditions found in tumors. In Aim 2, we will use droplet-based microfluidics systems to develop a high-throughput T cell killing assay that allows us to perform pooled CRISPR screens for the identification of genes that influence the cytotoxic capacity of T cells. In Aim 3, we will validate a subset of “candidate genes” identified Aim 1 and 2 in both human T cells as well as in murine tumor models. This proposal combines state-of-the-art genetic screening with innovative methods to analyze biologically meaningful T cell phenotypes and has the potential to reveal new targets for immunotherapy.

Informazioni aggiuntive

Acronimo
CRISPR
Data d'inizio
01.03.2021
Data di fine
28.02.2025
Durata
48 Mesi
Enti finanziatori
SNSF
Stato
In corso
Categoria
Swiss National Science Foundation / Project Funding / Division III - Biology and Medicine