GPC3 overexpression

This study uncovered TiME heterogeneity among GC patients with different MMR states, highlighting that the pMMR TiME is distinguished by hypoxia, pro-angiogenesis, and ECM remodeling, driven by the presence of GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells. These findings are pivotal for developing targeted immunotherapies for GC patients with pMMR.

GPC-3's re-expression in HCC and its involvement in key tumorigenic processes underscore its value as a biomarker for early diagnosis and a target for therapeutic intervention. Further research is warranted to fully exploit GPC-3's diagnostic and therapeutic potential in HCC management.

P1/2, N=110, Recruiting, Sotio Biotech Inc. | Trial completion date: Jul 2039 --> Dec 2041 | Trial primary completion date: Jul 2024 --> Apr 2026

Three HLA-A2-restricted GPC3 antigenic peptides were synthesized, with GPC3 FLAELAYDL and GPC3 FLIIQNAAV antigenic peptide-modified DCs inducing CTL production, and exhibiting strong targeted killing ability in LUSC cells at 80 : 1 multiplicity of infection. GPC3 may advance the onset and progression of LUSC, and GPC3 FLAELAYDL and GPC3 FLIIQNAAV antigenic peptide-loaded DC-induced CTLs have a superior killing ability against LUSC cells.

GCP-3 could be used as a biomarker in HCC diagnosis and prognosis, especially in evaluated diagnostic value in combination with AFP or GP73, and in forecasting worse survival data of overexpression GPC-3. https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022351566].

Our study shows that GPC3 overexpression is a poor prognostic factor in HCC. GPC3 positivity were found to be an independent risk factor for survival.

GPC3 cleavage in hepatoblastoma (HB) has a role in cell migration and proliferation with therapeutic potential. Use of furin inhibition is not an appropriate target for HB due to increased migration with the potential to enhance metastasis.

P1/2, N=98, Recruiting, SOTIO, LLC | Not yet recruiting --> Recruiting

P1/2, N=98, Not yet recruiting, SOTIO, LLC | Initiation date: Jan 2022 --> Apr 2022

STK-009 treatment resulted in significant expansion of SYNCAR-002 and drove infiltration of SYNCAR-002 into tumors. STK-009 treatment also induced intratumoral granzyme B+ and IFN-γ+ production by SYNCAR-002 indicating activation of effector T cell function.These findings validate that the orthogonal IL-2 platform has the potential to improve the efficacy and durability of CAR T therapy for solid tumor targets such as GPC3 by selectively expanding CAR-T cells in vivo, driving CAR-T cells into the tumor, and activating CAR-T cells in the tumor microenvironment.

Immunofluorescence staining of human liver specimens demonstrated specific binding to HCC versus cirrhosis with 79% sensitivity and 79% specificity, and normal liver with 81% sensitivity and 84% specificity. The near-infrared peptide is promising for early HCC detection in clinical trials.

P1/2, N=98, Not yet recruiting, SOTIO, LLC

The single chain antibody gene was cloned into vector for prokaryotic expression and purified to obtain high purity protein. Detection shows that the single-chain antibody produced by us has the same binding activity with the full-length antibody, and can accurately target the tumor site of Huh7 tumor-bearing model mice after coupling Cy5.5 fluorescence, suggesting that the single-chain antibody has the potential to realize multi-directional liver cancer precise surgical navigation under the guidance of a probe.

The IC of viscidulin I on SK-Hep1-GPC3 cells was 18.01 μM in cell proliferation assay. Thus, this method can be applied to screen complex herbal medicines for ligands bound to specific target protein receptor related to hepatic carcinoma.