South Korea has experienced FMD outbreaks almost every year since 2014. Therefore, a novel local vaccine that can cover various topotypes of viruses is required. Two virus strains, O/Boeun/SKR/2017 and A/Yeoncheon/SKR/2017, were cultured up to the pilot scale based on the optimized conditions set up on the flask scale. FMDV particles (146S) of 2 µg/mL or more were obtained from the virus culture supernatant using a 100 L bioreactor. The viruses were fully inactivated using binary ethylenimine within 16 h through two inactivation cycles and mixed with an adjuvant into a bivalent vaccine (types O and A) consisting of 15 µg viruses per strain. The experimental bivalent vaccine showed a broad spectrum of high neutralizing antibody titers against heterologous viruses, including type O Cathay strain and type A Asia topotypes, except for GVII. The 50% protective dose was determined as 12.5 for O/Boeun/SKR/2017 and 15.6 for A/Yeoncheon/SKR/2017. Collectively, we expect that the bivalent vaccine could protect against FMDV types O and A circulating in South Korea and neighboring countries. To our knowledge, this is the first report demonstrating that the vaccine strains could be successfully scaled-up to a 100 L bioreactor, with the determination of its protective efficacy in pigs.

Since the huge success of PD-1 blocking antibodies in clinical studies, anti-cancer therapy has changed its strategic gear to immunotherapy, which showed the strongest potential to eradicate cancer without detrimental side effects. Antibodies targeting similar immune checkpoint proteins with immunosuppressive functions have started to surge into clinical trials. CEACAM1 (CCM1) is also a potential target for anti-cancer immunotherapy because it is an ITIM-containing inhibitory molecule expressed on activated T cells and NK cells, on which it suppresses T/NK cell-mediated pro-inflammatory immune responses. CCM1-CCM1 homophilic interaction inhibits ZAP-70 phosphorylation in the TCR proximal signaling complex, thereby suppressing T cell activation. The anti-cancer therapeutic potential of CCM1-blockade has already been demonstrated in mouse models and one of the anti-human CCM1 antibodies entered into a phase I clinical trial once. As previously reported, our clone C25 (an anti-CCM1 monoclonal antibody) activated T cells and enhanced T/NK cell-mediated tumor cell-killing in a CCM1-dependent manner. The clone C25 was further engineered to have higher efficacies through mutagenesis within the variable regions of heavy and light chains. Here, we describe mutated variants of C25 with improved in vitro tumor-killing efficacies as well as higher binding affinities while maintaining fundamental characteristics of their parental clone C25. Most importantly, C25 and its variants exclusively bind to CCM1, but not to any other homologs of the CCM family. Such strong target-specificity will be a crucial point that distinguishes our clones from the other anti-CCM1 antibodies having off-target binding activities. We are currently investigating the CCM1-dependent anti-cancer therapeutic efficacy of our final clone on the patient-derived tumor xenografts implanted in a humanized mouse model. The target-ligand expression profiling on tumor tissues from lung cancer patients revealed strong clues for patient selection criteria and co-treatment options. Citation Format: So-Young Eun, Mijung Lee, Hye-Young Park, Miyoung Oh, Hye In Yum, Aerin Yoon, Eunhee Lee, Hyemi Nam, Sungtae Yun, Hyunjung Cho, Minkyu Hur, Jaehwan Kim, Byoung Chul Cho, Jonghwa Won. Enhanced anti-tumor efficacy of CEACAM1-targeting antibody after affinity maturation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-113.