Human TIGIT Antibody - Etiligimab Biosimilar

Human IgG1 monoclonal antibody (mAb) against human TIGIT

Anti-hTIGIT-hIgG1 is a recombinant monoclonal antibody (mAb) featuring a variable region that recognizes human TIGIT, and the constant region of the human IgG1 (hIgG1) isotype.  

TIGIT (T cell immunoglobulin and ITIM domain) is an inhibitory checkpoint that has been implicated in tumor immunosurveillance [1]. TIGIT is specifically expressed on immune cells including, natural killer (NK) cells and a range of T cell subsets. TIGIT binds to CD155 (PVR) and CD112 (PVRL2, nectin-2), which are expressed on antigen-presenting cells (APCs), T cells, and a variety of non-hematopoietic cells including tumor cells. Interestingly, TIGIT competes with CD226 (also known as DNAM-1) and CD96 (also known as Tactile) for the same ligands [1,2]. Upon binding to its ligand, phosphorylation of TIGIT inhibits the NF-κB, P13K, and MAPK pathways, and leads to a strong reduction of NK cytotoxicity as well as inhibition of T cell activation, proliferation, and effector functions [2,3]. 

The blockade of TIGIT is highly favorable in cancer immunotherapy due to a number of reasons including its low expression in peripheral lymphoid organs and high expression in tumor-infiltrating lymphocytes (TILs), the established synergy of TIGIT with other co-inhibitory immune checkpoints, and its ligands being widely expressed on tumor cells [1,2]. The dual blockade of TIGIT and PD-L1 has shown synergistic effects in a murine tumor model, resulting in complete tumor rejection and induced protective memory responses. A similar synergistic effect has been noted with PD-1 and Tim-3 [1,2]. Interestingly, TIGIT’s role in the tumor microenvironment (TME) may also be intertwined with the microbiome. The suppressive function of TIGIT is also exploited by a bacterium commonly found in the TME Fusobacterum nucleatun, to inhibit protective immune responses [4].

Features of Anti-hTIGIT-hIgG1:

• Targets specifically human TIGIT
• Features the hIgG1 constant region for high effector function
• Functionally validated by flow cytometry

Anti-hTIGIT-hIgG1 contains the human IgG1 constant region, which is known to bind with high affinity to the Fc receptor on phagocytic cells. Therefore, Anti-hTIGIT-hIgG1 displays high effector function, including antibody‑dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Anti-hTIGIT-hIgG1 was generated by recombinant DNA technology, produced in CHO cells, and purified by affinity chromatography with protein G.

References:

1. Solomon, B. L. et al, 2018. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother 67, 1659-1667.
2. Anderson, A.C. et al. 2016. Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity 44, 989-1004.
3. Joller, N. et al. 2011. Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. J Immunol 186, 1338-1342.
4. Gur, C. et al. 2015. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42, 344-355.