The bispecific antibody teclistamab was recently studied for resistance, with variant R27P mediating antigen escape (PMID 37653344). Resistance emerges after 9 months in most patients. Our binder B10, with a different predicted binding interface, enabled #aiCART cells to kill BCMA-R27P cells. (6)

Next, we used the #GenerativeAI tool RFdiffusion (PMID 37433327) from the Baker lab to design DNBs against BCMA, a key target in CAR-T therapy. After in vitro characterization in the CAR-T context, we selected the lead candidate (B10) and demonstrated in vivo activity in a #myeloma mouse model. (4)

We initially tested an in silico generated de novo binder (DNB) from the Baker Lab targeting EGFR (PMID 35332283). In a CAR construct, this binder performed well- killing cancer cell lines and patient-derived pancreatic cancer #organoids & forming immunological synapses with target cells. (3)

Cancer escapes immunotherapies by mutating its surface, meaning even groundbreaking #CARTCell therapies fail too often. But what if #GenerativeAI could design CAR-T with de novo binders faster, targeting resistant tumors? 🧵 www.biorxiv.org/content/10.1... (1)