Next-IO™ Anti-KLRG1 Monoclonal Antibody Program
Comparing to conventional cancer therapies, i.e. surgery, radio, and chemotherapies, monoclonal antibody-based therapies are highly advantageous because of their high affinity and specificity natures. To further elaborate, it is desired because mAb is able to recognize a specific and well-defined target. Immune checkpoints on immune cells are one of the popular targets because it induced significant clinical outcomes when reacting with anti-PD-1/L1 or CTLA4 antibodies. Creative Biolabs is dedicated to providing a variety of immuno-oncology programs to develop novel therapeutic antibodies with a goal to treat cancers. This program aims to develop the therapeutic monoclonal antibody against KLRG1 - an immune checkpoint expressed on NK cells.
KLRG1
Killer cell lectin-like receptor G1 (KLRG1), by name, is a C-type lectin inhibitory receptor and also an immune checkpoint expressed on certain T cells and NK cells. The ligands for KLRG1 are from the cadherin family, such as E-cadherin and N-cadherin and R-cadherin (see Fig.1). KLRG1 has an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the intracellular domain.
Relevance to Cancer
Upon binding to the ligands, E-cadherin, the cytoplasmic tail of KLRG1, will enroll signaling molecules, SHP-2 and SHIP-1, and produce inhibitory signals to the NK cells and T cells (see Fig.2). Studies have indicated that KLRG1 engagement can suppress effector functions of NK cells.
From the thorough research on the mechanism of action of KLRG1 and other preliminary data, we propose that KLRG1 be a potential therapeutic target for cancer treatment.
Fig.1 Receptor-ligand pairs involved in natural killer (NK) cell recognition of HER2+ breast cancer cell lines.1
Our Anti-KLRG1 Antibody Program
Our anti-KLRG1 mAb program aims to develop the novel therapeutic mAb against KLRG1 in the cancer immunotherapy. Since KLRG1 is broadly expressed in the subset T cells and natural killer (NK) cells, we are hoping to explore its anti-tumor effects in the different immune pathways. With the rich experience and understanding of therapeutic antibody discovery and development, Creative Biolabs is dedicated to offering strategic collaborations, together with our partners, to advance the program more efficiently. Except for the program on the monoclonal antibody, we also have combination strategies, or other antibody modalities, such as bispecific antibody, etc. that can cover the full spectrum of cancer immunotherapies targeting KLRG1. Please reach out to our scientists for consultation or discussion on how we can co-develop the therapeutic programs targeting KLRG1 in partnership.
Published Data
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Research on blood lymphocyte subset found greater KLRG1 expression in CD8 T and NK cells than CD4 T cells, and the difference is distinct to the expression on the CTLA-4 and PD-1 subsets.
Fig.2 Research on blood lymphocyte subset.2
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The gene expression of KLRG1 is correlated with the cytotoxic potential of CD8+ T cells.
Fig.3 The gene expression of KLRG1 is correlated with the cytotoxic potential of CD8+ T cells.2
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Co-inhibitory receptor, KLRG1, and its ligands, cadherin, are highly expressed in tumor cells.
Fig.4 Co-inhibitory receptor, KLRG1, and its ligands, cadherin, are highly expressed in tumor cells.2
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Anti-KLRG1 antibody therapy (alone or in combination with anti-PD-1 therapy) shows anti-tumor efficacy in an animal model with colon cancer.
Fig.5 Anti-KLRG1 antibody therapy shows anti-tumor efficacy in an animal model with colon cancer.2
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Anti-KLRG1 and anti-PD-1 combination therapy shows anti-tumor efficacy in an animal model with melanoma cancer.
Fig.6 Anti-KLRG1 and anti-PD-1 combination therapy shows anti-tumor efficacy in an animal model with melanoma cancer.2
Based on these data, we believe KLRG1 can be a potential target to treat cancer and blocking KLRG1 (alone or in combination with other treatments) is a promising immunotherapeutic strategy.
Program Planning and Management
We have extensive experience in performing comprehensive program developments and effective problem-solving. For our Next-IO™ programs, we are committed to delivering the program to the pre-IND stage within about 1.5 years. Accurate timeline will be determined on a case-by-case basis. Here is a draft timeline for your glance.
Fig.7 The timeline of Next-IOᵀᴹ programs.
Collaboration
Creative Biolabs is seeking potential partners to co-develop the cancer immunotherapies targeting KLRG1. With our skilled scientists and over a decade of CRO experience in the field, we believe we can develop the unique Next-IO™ programs! Please contact us for more information and a detailed quote.
References
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Muntasell, Aura et al. "Interplay between natural killer cells and anti-HER2 antibodies: perspectives for breast cancer immunotherapy." Frontiers in immunology. (2017) 8 1544.
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Greenberg, Steven A et al. "Co-inhibitory T cell receptor KLRG1: human cancer expression and efficacy of neutralization in murine cancer models." Oncotarget. (2019). 10,14 1399-1406.
For Research Use Only | Not For Clinical Use
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