AACR 2022: B-hIL12A/hIL12B/hIL12RB1/hIL12RB2: A Novel Animal Model for Generation of IL12 Therapies

AACR 2022: B-hIL12A/hIL12B/hIL12RB1/hIL12RB2: A Novel Animal Model for Generation of IL12 Therapies

Conclusions

• We successfully established a novel B-hIL12A/IL12B/IL12RB1/IL12RB2 multi-gene humanized mice that expresses human IL12A, IL12B, IL12RB1 and IL12RB2, whose CD4+ T cells specifically respond to human IL12 to produce IFN-γ.
• Leukocyte and T cell subpopulations from spleen, lymph nodes and blood in humanized B- hIL12A/hIL12B/hIL12RB1/hIL12RB2 mice showed overall development, differentiation and distribution patterns comparable to wild-type C57BL/6 mice.
• Blood cell composition, morphology and the levels of ALT, AST and other indicators in B-hIL12A/hIL12B/hIL12RB1/hIL12RB2 mice were comparable to the wild-type counterpart.
• In vivo efficacy evaluation of modified human IL12 showed significant anti-tumor activity in B-hIL12A/hIL12B/hIL12RB1/hIL12RB2 mice bearing syngeneic MC38 colon cancer cells.
• B-hIL12A/hIL12B/hIL12RB1/hIL12RB2 humanized mice provide a powerful preclinical model for in vivo evaluation of human IL12 therapies in diseases such as cancer and auto-immune diseases.