LAUSR

Immune checkpoint blockade became the most powerful way to control cancer without causing tremendous side effects, since anti-PD-1 blocking antibodies proved their superiority in clinical outcomes to those of traditional chemo- or targeted therapeutics. CEACAM1 (CCM1) is one of the several immune checkpoint receptors expressed on T cells that mediate suppression of inflammatory T cell response. CCM1 caught our attention for a cancer immune-therapeutic target, because of its inhibitory role in TCR proximal signaling complex. The anti-cancer therapeutic potential of CCM1-blockade has already been studied in mouse models, and one of the anti-human CCM1 antibody clones recently emerged in clinical Phase I studies. CCM1-targeting antibody candidates were screened out of our in-house synthetic libraries, among which a few of the clones stood out showing their significant blocking activities against CCM1-CCM1 homophilic interaction, enhancement of T cell activation, cytokine release, NFAT signaling, and tumor lysis. One of the clones (C25) showed its strongest efficacy equivalent to that of a reference Ab in CCM1-dependent T cell activation, proliferation, and IL-2 release, in parental Jurkat cells as well as in CCM1-overexpressing stable Jurkat cells. Moreover, C25 also enhanced tumor lysis by CCM1+ NK cells or CCM1+ cytotoxic T cells in a CCM1-dependent manner. In addition, C25 shows distinct characteristics in binding to CCM family from those of a reference Ab. Thus, C25 is thought to have a strong therapeutic potential on CCM1+ cancer. Citation Format: So-Young Eun. CEACAM1-blockade for T-cell activation and antitumor T-cell response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1645. doi:10.1158/1538-7445.AM2017-1645