In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5622-5622
Abstract:
GITR (glucocorticoid-induced TNFR-related protein) is a member of tumor necrosis factor receptor superfamily, expressed on many kinds of cells including T cells, attracting attention as a co-stimulatory immune checkpoint molecule. GITRL, the ligand of GITR is mainly expressed on antigen presenting cells. GITR/GITRL interaction plays an important role on the development of immune response, which can serve as promising anti-tumor target. While more than twenty anti-GITR antibodies are at clinical stages, combination treatments of GITR agonist and PD-1 inhibitor may be a better choice. Thus, there is a need for pre-clinical mouse model to evaluate the anti-tumor effect of humanized PD1/GITR antibodies. Gempharmatech established PD1/GITR double humanized mouse line on a BALB/c background, in which the extracellular domain of mGITR was replaced with its human counterparts while the trans-membrane and cytoplasmic domain kept intact, as well as the same strategy of PD1. BALB/c-hPD1/hGITR mouse could successfully express similar levels of hGITR and hPD1 compared with BALB/c wild type mice. Moreover, no immune or developmental abnormalities were observed in the humanized mouse. Anti-GITR combination with anti-PD1 presented greater tumor growth inhibition than anti-PD1 or anti-GITR monotherapies in PD1/GITR double humanized mouse bearing CT26 tumors. In summary, BALB/c-hPD1/hGITR are valuable models for the pre-cilincal evaluation of candidate humanized PD1/GITR combination treatment or bispecific antibody therapies. Citation Format: Dongdong Yuan, Dongdong zhang, Hongyan Sun, Mingkun Zhang, Liyou Dong, Cunxiang Ju, Shuai Li, Huiyi Wang, Jing Zhao, Xiang Gao. Preclinical evaluation of humanized PD1/GITR combination therapy using double humanized mouse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5622.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2022-5622
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2022
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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