Anti-NOG monoclonal antibody Made to order

NOD/Shi-scid/IL-2Rnull (NOG) mice are humanized with CD34+ hematopoietic cells (huNOG mice) and are commonly utilized for biological or medical research on human therapeutics. In the present study, nine 26-week-old, female huNOG mice were utilized for testing proprietary immune-modulating drugs over a 3-week period at the University of Washington. Two of the 9 mice developed unilateral swelling of a tibiotarsal joint with associated paresis of the affected limb. Full necropsies were performed after euthanasia at experimental end point, and routine tissues and affected tibiotarsal joints were evaluated. An expansile, multilobular mass composed primarily of chondroid cells associated with the calcaneal tendon was present within 1 tibiotarsal joint of both mice. A small focus of well-differentiated bone was present within the mass of 1 mouse. In addition, the calcaneal periosteum was expanded by a chondroid mass in 1 mouse. The cartilaginous masses associated with the calcaneal tendon were interpreted as a hyperplastic or low-grade neoplastic process accompanied by endochondral ossification, and the mass associated with the calcaneal periosteum was interpreted as chondroid metaplasia. Although the etiology of these lesions is unclear, their prevalence in 2/9 (22%) huNOG mice is interesting and may have biological significance for future studies involving the huNOG mouse model.

Purpose: Humanized mouse models using NOD/Shi-scid-IL2r gamma(null) (NOG) and NOD/LtSz-scid IL2r gamma(null) (NSG) mouse are associated with several limitations, such as long incubation time for stem cell engraftment and the development of xenograft versus host disease in mice injected with peripheral blood mononuclear cells (PBMCs). To solve problems, we used humanized major histocompatibility class I- and class II-deficient NOG mice (referred to as NOG-dKO) to evaluate the antitumor effect of anti-programmed death-1 (PD-1) antibody. Experimental Design: Humanized NOG-dKO mice, in which human PBMCs and human lymphoma cell line SCC-3, or glioblastoma cell line U87 were transplanted, were used as an immunotherapy model to investigate the effect of anti-PD-1 antibody. A biosimilar anti-PD-1 mAb generated in our laboratory was administered to humanized NOG-dKO mice transplanted with tumors. Results: Within 4 weeks after transplantation, human CD45(+) cells in antibody-treated mice constituted approximately 70% of spleen cells. The injection of anti-PD-1 antibody reduced by more 50% the size of SCC-3 and U87 tumors. In addition, induction of CTLs against SCC-3 cells and upregulation of natural killer cell activity was observed in the antibody-treated group. Tumor-infiltrating lymphocyte profiling showed that more exhausted marker (PD1(+)TIM3(+)LAG3(+)) positive T cells maintained in anti-PD-1 antibody-treated tumor. A greater number of CD8(+) and granzyme-producing T cells infiltrated the tumor in mice treated with the anti-PD-1 antibody. Conclusions: These results suggest that NOG-dKO mice might serve as a good humanized immunotherapy model to evaluate the efficacy of anti-PD-1 antibody prior to the clinical treatment. (C) 2016 AACR.