Yufei Wang, Alicia Buck, Brandon Piel, Luann Zerefa, Nithyassree Murugan, Christian D Coherd, Andras G Miklosi, Haraman Johal, Ricardo Nunes Bastos, Kun Huang, Miriam Ficial, Yasmin Nabil Laimon, Sabina Signoretti, Zhou Zhong, Song-My Hoang, Gabriella M Kastrunes, Marion Grimaud, Atef Fayed, Hsien-Chi Yuan, Quang-De Nguyen, Tran Thai, Elena V Ivanova, Cloud P Paweletz, Ming-Ru Wu, Toni K Choueiri, Jon O Wee, Gordon J Freeman, David A Barbie, Wayne A Marasco
One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues...
March 16, 2024: Molecular Cancer