Next-IO™ Anti-SOCS3 Therapeutic Monoclonal Antibody Program

About This Program

This program aims to develop an anti-SOCS3 therapeutic monoclonal antibody for immuno-oncology.

Cytokine signaling inhibitory factor (SOCS) is a protein that negatively regulates the JAK/STAT pathway. Among all the SOCS proteins, the CIS, SOCS1 and SOCS3 sub-proteins are considered as the third-ranking immune checkpoint molecule following PD-1 and CTLA4, which modulates CD4⁺ T cell polarization and cytokine signaling of CD8⁺ T cell maturation, respectively. Most cytokines play roles in the activation and regulation of immune responses through the JAK/STAT signaling pathway. And SOCS3, in specific, terminates JAK/STAT signaling pathway by inhibiting the activation of STAT1 and STAT3, suggesting the mechanism of action for SOCS in immunotherapy.

SOCS3

SOCS protein family shares similar structure: a N-terminal region of variable length and highly variable amino acid sequence, a central SH2 domain, and a striking region of a carboxyl-terminal 40-amino acid module called the SOCS box. The SOCS cassette binds to the E2 ubiquitin protein-transfer enzyme and mediates degradation of proteins that are associated with SOCS family members through N-terminal and SH2 regions. A variety of studies have shown that SOCS3 is an anti-cancer gene:

Fig.1 General mechanism of the action of CIS, SOCS1, and SOCS3.¹

SOCS3 in Cancer Studies

Here are some published data about SOCS3 working as a potential target for cancer immunotherapy.

• Myeloid-specific SOCS3 loss promotes tumor growth and is associated with lower OS rates.

Fig.2 The tumor size (left) and the Kaplan-Meier plots (right) showed that myeloid-specific SOCS3 loss promotes tumor growth and patients with positive tumor SOCS3 expression had a better OS rate.^2,3

• SOCS3 suppresses proliferation of colorectal cancer cells in vivo.

Fig.3 Tumor size of the knockdown (above) or overexpression (below) of SOCS3.²

Ongoing Clinical Trials

• Currently, as far as we know, NO anti-SOCS3 therapeutic monoclonal antibodies are being evaluated in clinical trials.
• Despite this, SOCS3 is still a compelling target for cancer immunotherapy. In an effort to optimally leverage SOCS3-mediated immune response, our next generation of SOCS3 targeting treatment attempts to explore combination therapy trials by involving other immunomodulatory agents.

Program Planning and Management

We have 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.

Fig.4 Project pipeline management of therapeutic monoclonal antibody.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-SOCS3 therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership. For any partners interest 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 advance their programs with more chance to succeed. Look forward to cooperating with you in the near future.

References

• Chikuma, S.; et al. Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy. Cancer Science, 2017, 108(4): 574-580.
• Chu, Q.; et al. Prognostic significance of SOCS3 and its biological function in colorectal cancer. Gene. 2017, 627: 114-122.
• Yu, H.; et al. SOCS3 deficiency in myeloid cells promotes tumor development: involvement of STAT3 activation and myeloid-derived suppressor cells. Cancer Immunol Res. 2015, 3(7): 727-740.