The effects of the CTLA4 deletion were not very surprising, what's fascinating here is how it compares to the double mutants (PD1/CTLA4).

"CTLA4 disrupted CART19 cells display prolonged surface CAR expression, increased proliferation, and enhanced CART19 effector function supported by unopposed CD28 co-stimulation, which is lost in CART19 cells deficient for both PD-1 and CTLA4"

#Immunology #Immunotherapy #CheckpointInhibitor #CTLA4 #CARTcells

https://www.cell.com/immunity/fulltext/S1074-7613(23)00407-7#secsectitle0075

Thirty years ago, in November 1992, Ishida, Honjo and their collaborators reported the discovery of the #PD1 gene in @embojournal

https://www.embopress.org/doi/abs/10.1002/j.1460-2075.1992.tb05481.x

I spoke with Tasuku Honjo, Pierre Golstein (whose team first cloned #CTLA4) & Facundo Batista about the discovery earlier this year.
The initial project had absolutely nothing to do with checkpoints or #immunotherapy

Listen to the full #EMBOPodcast episode at the link below or on pretty much any podcast app

#Immunology #HistoryScience #Cancer #CellDeath

https://www.embo.org/podcasts/from-cell-death-to-cancer-immunotherapy/

#Immunology #Immunotherapy
#checkpointinhibitors

"In this Review we mark the tenth anniversary of the approval of ipilimumab and discuss the foundational scientific history of ICB, together with the history of the discovery, development and elucidation of the mechanism of action of the first generation of drugs targeting the #CTLA4 and #PD1 pathways."

https://www.nature.com/articles/s41573-021-00345-8