Next-IO™ Anti-LAG-3 Therapeutic Monoclonal Antibody Program
About This Program
This program aims to develop anti-LAG-3 therapeutic monoclonal antibody for colorectal cancer immunotherapy.
Rationale for our program:
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Although CTLA4 and PD1-PDL1 have made breakthroughs in the treatment of advanced malignancies, most patients with many tumor types do not respond. Therefore, it is necessary to shift the focus to an in-depth study of the tumor microenvironment to find alternative therapeutic targets.
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Lymphocyte activating gene-3 (LAG3) (CD223) inhibits T cell activation and cytokine secretion, thereby ensuring immune homeostasis. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression.
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Studies have shown that LAG3 and PD1 have significant synergistic effects observed in a variety of disease settings, highlighting the potential uniqueness of LAG3.
Given the above, LAG3 is a promising immune checkpoint for clinical translation.
LAG-3
LAG-3 is a type I transmembrane protein of the immunoglobulin (Ig) superfamily. It is usually expressed in activated T cells, natural killer cells or B cells, and functionally negatively regulate the homeostasis of these cells. LAG-3 has been identified as a next generation of immunological checkpoint proteins that play a variety of roles in cancer immunity, including:
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Inhibition of Th1 cell proliferation, reduction of the production of interleukin (IL), interferon-gamma and tumor necrosis factor in T cells.
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The interaction of LAG-3 with MHC-II prevents the binding of the same MHC molecule to TCR and CD4, thereby inhibiting the TCR signal.
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Crosslinking of LAG-3 and CD3/TCR complexes can impair T cell proliferation, cytokine secretion, and calcium flux.
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LAG-3 together with other immune checkpoints inhibits T cell activation, especially PD-1.
Fig.1 LAG-3 signaling and interaction with other immune checkpoints. (Long, 2018)
Supporting Data
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Administration of LAG-3 antibody (LBL-007) alone can inhibit tumor growth, and the combination with anti-PD-1 antibodies results in a significant reduction in tumors in a mouse colorectal cancer model.
(Yu, 2019)
The data support the rationale for the development of the first-in-class human anti-LAG-3 with an improved therapeutic index for the treatment of CRC.
Colorectal Cancer
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CRC is one of the most common malignancies in humans. It is estimated that nearly 881,000 new deaths occurred in 2018, ranking second in cancer mortality.
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The global CRC drug market size estimate for 2018 is $994 million, and the compound annual growth rate is expected to be close to 3% between 2019 and 2023.
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The global immunotherapy market size for CRC in 2018 is estimated at 5 billion.
Ongoing Clinical Trials
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Currently, several anti- LAG-3 therapeutic monoclonal antibodies have been testing in preclinical and clinical trials. Combination strategies are also of interest, such as the combination of LAG3 with anti-PD1, anti-CTLA4, and IDO1 inhibitors, which are being tested in clinical trials.
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We believe that this novel targeting strategy will provide insights into the tumor immunotherapy, especially in the treatment of CRC cancer. In an effort to optimally leverage LAG-3-mediated immune response, our next-IO™ LAG-3 targeted antibody program attempts to explore the optimal combination therapy trials by involving other immunomodulatory agents, particularly immune checkpoints.
Program 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.
Cooperation
Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop LAG-3 therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing 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 chances to succeed. Look forward to cooperating with you in the near future.
References
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Long, L.; et al. The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes & cancer. 2018, 9(5-6): 176.
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Yu, X.; et al. Characterization of a novel anti-human lymphocyte activation gene 3 (LAG-3) antibody for cancer immunotherapy. MAbs. 2019, 11(6): 1139-1148.
For Research Use Only | Not For Clinical Use