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SITC20 Poster 245: New hTLR8 Knock-In Mouse Model for Enhanced Immunotherapy Studies

Human TLR8 Knock-In Mice Potentiate Immunotherapy Responses of MC38 Syngeneic Tumors

Shanshan Qi, Hongjuan Zhang, Ruilin Sun*, Annie X. An, Henry Q.X. Li, Davy X. Ouyang
*Shanghai Model Organisms Center, Inc., China
SITC20 Poster 245: New hTLR8 Knock-In Mouse Model for Enhanced Immunotherapy Studies
Improved understanding of toll-like receptor 8 (TLR8) is needed to fully elucidate its role in inflammation and tumor progression. Advanced preclinical models are needed to achieve this understanding, due to the different functions of human and mouse TLR8. Human TLR8 recognizes single-stranded self-RNA, viral RNA, and synthetic small molecule agonists, while mouse Tlr8 is non-functional due to the absence of 5 amino acids necessary for RNA recognition.

This poster details the development and characterization of a human knock-in TLR8 mouse model, where exon 3 of mouse Tlr8 was replaced with the human counterpart. The potential applications of hTLR8 mice for cancer immunotherapy studies were also assessed.

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  • That hTLR8 mediated pro-inflammatory immune response synergizes anti-mPD-1 checkpoint inhibitor immunotherapy, converting cold tumors into hot tumors

  • How increased liver weight and decreased lymphocytes and neutrophils in blood circulation were observed in the hTLR8 group

  • Why hTLR8 knock-in mice may be an interesting host strain for syngeneic tumor studies

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