Next-IO™ Anti-GPC3 Therapeutic Monoclonal Antibody Program

About This Program

This program aims to develop anti-GPC3 therapeutic monoclonal antibodies for immuno-oncology.

Glypicanin-3 (GPC3) is a heparan sulfate proteoglycan, expressing mostly in hepatocellular carcinoma (HCC), ovarian clear cell carcinoma, melanoma, lung squamous cell carcinoma, hepatoblastoma, kidney blastoma, and some pediatric cancers. To note, GPC3 is currently used as a diagnostic biomarker to distinguish HCC from normal liver tissues, benign liver tumors, and other types of metastatic cancer, highlighting the rationale for GPC3-based tumor immunotherapy.

GPC3

GPC3 can be immobilized on the cell surface by glycosylphosphatidylinositol anchors. GPC3 can be expressed in a variety of tissues during embryonic development. Beyond that life state, it is a highly tumor-specific antigen in which expression is severely inhibited in most adult tissues.

Highlighted Functions:

Elevated GPC3 expression is reported in a variety of tumor types, such as liver, lung, stomach, ovarian, esophageal, and other forms of cancer, meaning GPC3 is an ideal target to be studied in patients with solid tumors.
In particular, GPC3 is currently used as a diagnostic biomarker to distinguish HCC from normal liver tissues, benign liver tumors, and other types of metastatic cancer.
There is sufficient evidence to suggest GPC3 is involved in the malignant transformation of HCC.

Fig.1 Cancer immunotherapy targeting GPC3. (Shimizu, 2019)

GPC3 in Cancer Studies

Here are some published data about GPC3 working as a potential target for cancer immunotherapy.

GPC3 expression is associated with worse overall survival rate, compared to GPC3-negative cases of HCC.

Anti-GPC3 Therapeutic Monoclonal Antibody Program (Shimizu, 2019)

GPC3 antibody (HN3 and HS20) inhibits tumor growth in GPC3-expressing liver cancer.

Anti-GPC3 Therapeutic Monoclonal Antibody Program (Gao, 2015)

Ongoing Clinical Trials

Currently, only two anti-GPC3 therapeutic monoclonal antibodies are being evaluated in clinical trials. Cumulative preclinical data demonstrate its important role in cancer progression; however, safety, efficacy, and combination strategies require further confirmation.

Trial	Patients	ID
A randomized, placebo-controlled, double-blind, multicenter phase II trial of intravenous GC33 at 1,600 mg Q2W in previously treated patients with unresectable advanced or metastatic HCC	Histologically confirmed HCC	NCT 01507168
A phase I dose escalation and cohort expansion study of ERY974, an anti-GPC3/CD3 bispecific antibody, in patients with advanced solid tumors	Patients with GPC3-positive advanced solid tumors not amenable to standard therapy or for which standard therapy was not available or not indicated	NCT 02748837

Table1. Clinical trials for cancer immunotherapy targeting GPC3. (Front Oncol, 2019)

There is enough evidence to support GPC3 as a compelling target in cancer immunotherapy. In an effort to optimally leverage GPC3-mediated immune response, our next generation of GPC3 targeting treatment attempts to explore combination therapy by involving it with other immunomodulatory agents.

Program Planning and Management

Creative Biolabs has extensive knowledge of end-to-end program development. For each program, we are committed to delivering the final complete program to our clients within 1.5 years before entering the IND stage.

Anti-GPC3 Therapeutic Monoclonal Antibody Program

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-GPC3 therapeutic monoclonal antibody programs together. Our scientists are dedicated to bringing together years of valuable experience to our partner and achieve a meaningful partnership together. For any partners interested in our Next-IO™ programs, Creative Biolabs welcomes collaboration.

Here are two ways for your choice, and please contact us for more details.

1) Collaborate with us and co-develop the programs from the discovery phase to IND enabling. Costs will be shared.
2) Become a licensed candidate for our programs.

With our quality control protocol and knowledge of global regulatory requirements, we can help our partners further their programs with more chance to succeed. Look forward to cooperating with you in the near future.

References

Shimizu, Y.; et al. Next-generation cancer immunotherapy targeting glypican-3. Frontiers in oncology. 2019, 9: 248.
Zhang, Y.; et al. Delta-like 3 expression in gastrointestinal neuroendocrine tumors portends new therapeutic options. Gastroenterology. 2017, 152(5): S669.
Shimizu, Y.; Nakatsura, T. Glypican-3: Hepatocellular carcinoma specific antigen, a novel target for cancer immunotherapy. Glycoforum. 2019, 22: A1.
Gao, W.; et al. Human monoclonal antibody targeting the heparan sulfate chains of glypican-3 inhibits HGF-mediated migration and motility of hepatocellular carcinoma cells. PloS one. 2015, 10(9): e0137664.

For Research Use Only | Not For Clinical Use