Transgenic expression of human signal regulatory protein alpha (SIRPα) in BALB/c Rag2 null /Jak3 null immunodeficient mice improves human lymphoma xenograft via reduction of phagocytosis

The immunodeficient mouse model provides a platform for assessing therapeutic options in preclinical cancer research by allowing the establishment of human xenografts. We previously developed BALB/c Rag2nullJak3null (BRJ), an immunodeficient mouse model valuable for cancer research. However, susceptibility to xenograft acceptance can be enhanced by the signal regulatory protein alpha (SIRP)-CD47 “don‘t eat me” signal. In this study, we created BALB/c human-SIRP BAC transgenic mice and crossed them with BRJ mice. The resulting human SIRP transgenic BRJ (BRJ-S) mice showed significantly increased engraftment of human B-cell lymphoma compared to BRJ mice. Additionally, we demonstrated improved human tumor engraftment in BRJ-S mice by reducing phagocytosis. In summary, hSIRP-transgenic BRJ mice (BRJ-S) serve as a promising immunodeficient model with a greater capacity for human lymphoma engraftment. BRJ-S provides an advantageous and permissive model for xenografting and for studying cancer in research and drug development.