Novel low‐avidity glypican‐3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC
Methods and Results New human glypican‐3 (hGPC3) mAbs were developed from
immunized mice. We obtained three hGPC3‐specific mAbs that stained HCC tumors, but not
the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33,
the frequently used high‐affinity mAb, but with approximately 17‐fold lower affinity. We then
compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor
effects. In vitro, low‐avidity 8F8 CARTs killed both hGPC3 high and hGPC3 low HCC tumor …
immunized mice. We obtained three hGPC3‐specific mAbs that stained HCC tumors, but not
the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33,
the frequently used high‐affinity mAb, but with approximately 17‐fold lower affinity. We then
compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor
effects. In vitro, low‐avidity 8F8 CARTs killed both hGPC3 high and hGPC3 low HCC tumor …