Anti-mTIGIT

Anti-mTIGIT-mIgG2a InvivoFit™ is an anti-mTIGIT monoclonal antibody featuring the variable region of the previously described 10A7 clone [1] and a murine IgG2a constant region.

TIGIT (T cell immunoglobulin and ITIM domain) is a cell surface inhibitory immune checkpoint [1]. It is specifically expressed on immune cells including Natural Killer (NK) cells, activated and memory T cells, as well as regulatory T cells (Tregs) [2].

The 10A7 mAb has been used to block TIGIT signaling in Tregs and chronically stimulated CD8+ T cells [3, 4]. Using recombinant technology, the original 10A7 hamster IgG2a constant region has been replaced with a murine IgG2a format which mediates potent cytotoxic functions [5]. This murinization also allows reduced immunogenicity of the administered mAb and risks for fatal hypersensitivity reactions [6-8].

Key features of Anti-mTIGIT-mIgG2a InvivoFit™:

• Derives from the 10A7 clone, Hamster IgG2a
• Features the mIgG2a isotype (constant region)
• Guaranteed sterile, endotoxin level < 1 EU/mg
• Suitable for parental delivery in mice (azide-free)
• Low aggregation < 5%
• Produced in animal-free facilities and defined media

Anti-mTIGIT-mIgG2a InvivoFit™ is produced in Chinese hamster ovary (CHO) cells, purified by affinity chromatography with protein A, and provided in an InvivoFit™ grade, a high-quality standard specifically adapted to in vivo studies. The binding of Anti-mTIGIT-mIgG2a InvivoFit™ to mouse TIGIT has been confirmed using Flow cytometry (see Figure).

References:

1. Yu X. et al, 2009. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 10(1):48-57.
2. Chauvin J.M. & Zarour H.M., 2020. TIGIT in cancer immunotherapy. J. Immunother. Cancer 8:e000957.
3. Jonhston R.J., et al,  2014. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell. 26(6):923-937.
4. Joller, N. et al,  2014. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity. 40(4):569-581.
5. Nimmerjahn F. & Ravetch J.V., 2005. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science. 310:1510-2.
6. Mall C. et al., 2016. Repeated PD-1/PD-L1 monoclonal antibody administration induces fatal xenogenic hypersensitivity reactions in a murine model of breast cancer. Onco Immunol. 5(2):e1075114.
7. Murphy, J.T.et al,  2014. Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice. Blood. 123:2172-80.
8. Belmar N.A. et al,  2017. Murinization and H chain isotype matching of Anti-GITR antibody DTA-1 reduces immunogenicity-mediated anaphylaxis in C57BL/6 mice. J Immunol. 198:4502-4512