Characterization of ASP8374, a fully-human, antagonistic anti-TIGIT monoclonal antibody

Cancer Treatment and Research Communications

卷:28

Gerald Koelsch¹  Cynthia Seidel-Dugan²  Makoto Ohori³  Kenna Shirasuna³  Masahiro Takeuchi³  Daniel J Hicklin³  Shingo Sugahara³  Christopher J Nirschl⁴  Sandra Abbott⁴  Heather R Brodkin⁴  Philipp Steiner⁴  Fumitaka Kinugasa⁴  Taku Yoshida⁴  Andres Salmeron⁴  William M Winston⁴ 

[1] Corresponding author.;

[2] Drug Discovery Research, Astellas Pharma Inc., 1 Astellas Way, Northbrook, IL 60062, USA;

[3] Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan;

[4] Potenza Therapeutics, 1030 Massachusetts Avenue, Suite 210, Cambridge, MA 02138, USA;

关键词: Cancer;    TIGIT;    Immune checkpoint;    Immunotherapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

The T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) is a validated immune checkpoint protein expressed on memory CD4+T-cellls, Tregs, CD8+T-cell and natural killer (NK) cells. ASP8374 is a fully human monoclonal immunoglobulin (Ig) G4 antibody designed to block the interaction of TIGIT with its ligands and inhibit TIGIT signaling. ASP8374 exhibited high affinity binding to TIGIT and increased interferon (IFN)-γ production of cultured peripheral blood mononuclear cells (PBMCs) in a titratable manner. When used in combination with pembrolizumab, an anti-programmed death-1 (PD-1) antibody, ASP8374 induced higher T-cell activation in vitro than either treatment alone. An anti-mouse TIGIT antibody surrogate, mSEC1, displayed anti-tumor efficacy in an MC38 syngeneic mouse tumor model alone and in combination with an anti-programmed death-ligand 1 (PD-L1) antibody. In an additional syngeneic mouse tumor model (CT26), while mSEC1 alone did not demonstrate anti-tumor efficacy, mSEC1 combined with an anti-PD-1 antibody enhanced anti-tumor efficacy above that of the anti-PD-1 antibody alone. These data provide evidence that ASP8374 has therapeutic potential for advanced malignancies.

【 授权许可】

Unknown