About This Program

This program aims to develop anti-ICOSL therapeutic fusion protein for immuno-oncology.

Inducible costimulatory molecules ligand (ICOSL) functions to activate the co-stimulatory receptor ICOS, thus enhancing T-cell-modulated immune responses. Previous studies have shown that the ICOS/ICOSL pathway may play an important role in CTLA4 inhibitor-induced tumor immunity. However, ICOS-ICOSL pathway is a complex central hub for immune response and homeostasis. Therefore, targeting ICOSL may lead to contrasting results.

ICOSL

Inducible costimulatory molecules (ICOS) are CD28-associated molecules expressed only on activated T cells. Its ligand-inducible costimulatory ligand (ICOSL) can be found in professional APCs such as dendritic cells (DC), B lymphocytes, and some cancer cells. ICOS/ICOSL axis has a dual effect and might participate in anti-tumour T cell response as well as a pro-tumour response due to its connection with regulatory T-cells (Tregs) suppressive activity (see Fig.1).

Highlights of ICOSL target as a promising for cancer therapy:

• ICOSL demonstrates a positive co-stimulatory effect by specifically modulating the responses from regulatory T cells (Treg) and Th2 cells
• The blockade of ICOSL significantly reduced the generation of Th2 cytokines including IL-4 and IL-10 but did not affect the expression of the Th1 cytokines such as IFN-γ and IL-2
• ICOSL expression in solid tumors aids in the activation of CD8+ cytotoxic T cells, thus triggering anti-tumor responses

ICOSL Fusion Protein in Cancer Studies

To the best of our knowledge, only one study showed that the ICOSL-Fc fusion protein enhances the proliferation and cytotoxicity of human T cells by increasing INF-γ and IL10 secretion, which was reported at the International Cancer Immunotherapy Conference in February 2019. Here are some published data about ICOSL functioning as a potential target for cancer immunotherapy.

• Kaplan–Meier curves for the overall survival of breast cancer patients in relation to ICOSL expression.

Fig.1 Kaplan–Meier curves for the overall survival of breast cancer patients in relation to ICOSL expression.¹

Clinical Trials under Progress

NO clinical trial of the ICOSL fusion protein is currently ongoing. Our program will be a pioneer in the development of ICOSL fusion proteins.

Program Plan

Creative Biolabs has established the novel chimeric fusion protein platform for Agonist Redirected Checkpoint (ARC) program development. 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 prior to entering the IND stage.

Fig.2 The timeline of Next-IOᵀᴹ programs.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-ICOSL therapeutic fusion protein program together. Our scientists are dedicated to bringing together years of valuable experience to our partner and achieve a meaningful partnership. By doing so, we wish to help both parties to proceed with IND and many stages of clinical trials beyond.

If you are interested, please feel free to contact us so that we can discuss the program and other possible opportunities for cooperation. Look forward to working with you in the near future.

Reference

• Wang, Bin et al. "Expression of ICOSL is associated with decreased survival in invasive breast cancer." PeerJ. （2019） 7 e6903.

For Research Use Only | Not For Clinical Use