Francesco Maura, Assistant Member at Memorial Sloan Kettering Cancer Center, shared on LinkedIn:
“New pre print from the lab out today on bioRxiv and medRxiv!!
Why does CD19 CART produce durable remission in only about a third of patients with relapsed large B-cell lymphoma, when most relapsed tumors still carry CD19?
To answer this question we expand out great collaboration with Frederick Locke, Alexander Anderson, Jonathan Schatz interrogating WGS snd RNAseq from 54 LBCL patients before infusion and at progression. One of the most significant predictors of outcome was biallelic loss of MHC-I or CD58 (Bachisio Ziccheddu)
That is a paradox, because CAR-T killing does not require MHC-I. The resolution is that the CAR-T cells are not working alone. Across a mathematical model (Chandler Gatenbee ), B2m-knockout and CD8-knockout mouse models (Venu Venkatarame Gowda), 328,000 single cells (Abdessamad Youssfi Alaoui), and IFN-gamma ELISPOT in patients (Constanza Savid-Frontera), durable eradication required the patient’s own endogenous CD8 T cells. Mice cured by CAR-T went on to control CD19-negative rechallenge (Constanza Savid-Frontera).
Overall, these data suggest that CD19 CAR-T is not only a cytotoxic therapy, but a catalyst for the host antitumor immunity required to sustain remission and achieve cure.
Thanks again to all our collaborators, patients and funders.”
Title: Lymphoma response to chimeric antigen receptor T cell therapy is driven by endogenous tumor-reactive CD8⁺ T cells
Authors: Bachisio Ziccheddu, Constanza Savid-Frontera, Venu V.G. Saralamma, Chandler Gatenbee, Abdessamad A. Youssfi, Monika Chojnacka, Meghan Menges, Luis Cuadrado-Delgado, Michael Durante, John Mullinax, Keyla Reid, Julieta Abraham Miranda, Salvatore Corallo, Emily Merritt, William Sawyer, Anthony Augello, Austin D. Newsam, Dhanvantri Chahar, Catalina Amador, Jay Y. Spiegel, Marco Davila, Ola Landgren, Juan Pablo Alderuccio, Mark Robertson-Tessi, Reginald Atkins, Saad Usmani, Michael D. Jain, Alexander R.A. Anderson, Francesco Maura, Jonathan H. Schatz, Frederick L. Locke.
Other articles from Francesco Maura on OncoDaily.