June, 2024
June 2024
John Gordon: CART cells vs B cells Deliver a ‘Killer Punch’ to CAR-ve Onlookers 
Apr 21, 2024, 23:39

John Gordon: CART cells vs B cells Deliver a ‘Killer Punch’ to CAR-ve Onlookers 

John Gordon, Vice president of

“CART cells vs B cells Deliver a ‘Killer Punch’ to CAR-ve Onlookers  |
CART cell Therapy activates CD8+ Cytotoxic CARneg bystander Tcells in non-Human Primates and Patients | New Study by Ulrike Gerdemann and Co. |

CAR-T cells hold promise as a therapy for B-cell-derived malignancies, yet despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. While recent studies have explored the mechanisms of in vivo CAR-T cell function, little is understood about the activation of surrounding CARneg bystander T-cells and their potential to enhance tumor responses.

We performed single-cell RNA-Seq (scRNA-Seq) on non-human primate (NHP) and patient-derived T-cells to identify the phenotypic and transcriptomic hallmarks of bystander activation of CARneg T-cells following B-cell targeted CAR-T cell therapy.

Here* utilising a highly translatable CD20 CAR NHP model, the authors observed a distinct population of activated CD8+ CARneg T-cells emerging during CAR-T cell expansion. These bystander CD8+ CARneg T-cells exhibited a unique transcriptional signature with upregulation of NK-cell markers (KIR3DL2, CD160, KLRD1), chemokines and chemokine receptors (CCL5, XCL1, CCR9), and downregulation of naive T-cell-associated genes (SELL, CD28).

A transcriptionally similar population was identified in patients following Tisagenlecleucel infusion. Mechanistic studies revealed that IL-2 and IL-15 exposure induced bystander-like CD8+ T-cells in a dose dependent manner. In vitro activated and patient-derived T-cells with the bystander phenotype efficiently killed leukemic cells through a TCR-independent mechanism.

Collectively, this dataset provides the first comprehensive identification and profiling of CARneg bystander CD8+ T-cells following B-cell targeting CAR-T cell therapy and suggests a novel mechanism through which CAR-T cell infusion might trigger enhanced anti-leukemic responses.

OPEN ACCESS preprint can be found at bioRxiv and medRxiv.”John Gordon


Read further.
Source: John Gordon/LinkedIn

About OncoDaily

OncoDaily was founded in 2023. It is a US-based oncology media platform, which features the latest news, insights, and patient stories from the world of oncology. Within short period of time it became one of the leading oncology media platforms globally.

OncoDaily gathers content from various sources, including social media posts from renowned oncologists from all over the world, news from oncology societies and cancer centers, patient and survivor stories, and career-related information for professionals.

The mission of OncoDaily is to empower patients, survivors, and professionals with the knowledge and inspiration they need to fight cancer. The motto of OncoDaily is “Cancer doesn’t take a day off – neither do we.”