Transgenic expression of human signal regulatory protein alpha (SIRPα) in BALB/c Rag2null/Jak3null immunodeficient mice enhances human lymphoma xenografts by reducing phagocytosis

The immunodeficient mouse model offers a platform for evaluating therapeutic options in preclinical cancer research by enabling the growth of human xenografts. We previously developed BALB/c Rag2 null Jak3 null (BRJ), an immunodeficient mouse model useful for cancer studies. However, susceptibility to xenograft acceptance can be increased through signal regulatory protein alpha (SIRPα)-CD47 signaling, also known as the “don't eat me” signal. In this study, we generated BALB/c human-SIRPα BAC transgenic mice and crossed them with BRJ mice. The resulting human SIRPα-transgenic BRJ (BRJ-S) mice showed a significantly higher engraftment rate of human B-cell lymphoma than BRJ mice. Furthermore, we demonstrated better human tumor engraftment in BRJ-S mice by reducing phagocytosis. In summary, hSIRPα-transgenic BRJ mice (BRJ-S) serve as a promising immunodeficient model with enhanced capacity for human lymphoma engraftment. BRJ-S provides an advantageous and permissive model for xenografting and for studying cancer in research and drug development.