Description:
The current state of the art
The majority of liver cancers, the 2nd leading cause of cancer death among adult men, are hepatocellular carcinoma (HCC). About 70-80% HCC tumors, but not normal hepatocytes, express glypican 3 (GPC3), a cell surface antigen. Thus, GPC3 might be a great target for HCC immunotherapy, especially chimeric antigen receptor-modified T cell therapy (CART).
The limitation of the current art
The current CARTs against HCC target one epitope of GPC3. GC33 is the only mAb that has advanced to the clinical trial. But its efficacy is still being evaluated. Moreover, GC33 might have safety concerns because of binding to adjacent non-cancerous tissue. Therefore, there is an urgent need to develop effective GPC3 specific CARTs that target different epitopes of GPC3 for HCC immunotherapy.
The advantages of our invention:
Scientists at AU developed novel effective GPC3 specific chimeric antigen receptor-modified T cells that target different regions of human GPCs than GC33. Three (3) out twenty-two (22) identified mAbs were found to specifically bind HCC tumors but not adjacent normal tissues. The mAb’s affinity was in the nanomolar range. Two CARTs (6G11 and 8F8) built from mAbs, targeting the hGPC3 N- or C-specific epitopes, underwent extensive expansion by HCC cell stimulation and possessed strong effector function. Adoptive transfer of these two CARTs completely eradicates the tumors of HCC xenografts (Figure 1). Therefore, CARTs targeting the hGPC3 N- or C-specific epitopes have great potential for HCC immunotherapy.
AURI # 2019-018
Lead Inventor: https://augusta.pure.elsevier.com/en/persons/yukai-he/network/
IP status: US provisional 62,903776
Reference: https://pubmed.ncbi.nlm.nih.gov/34897774/