Siglec15/TGF-β bispecific antibody mediates synergistic anti-tumor response against 4T1 triple negative breast cancer in mice.

ABSTRACT: An ideal tumor-specific immunomodulatory therapy should both preferentially target the tumor, while simultaneously reduce the immunosuppressive environment within the tumor. This guiding principle led us to explore engineering Siglec-15 (S15) targeted bispecific antibody (bsAb) to enhance therapy against triple negative breast cancer (TNBC). S15 appears to be exclusively expressed on macrophages and diverse tumor cells, including human and mouse 4T1 TNBC. TGF-β is a growth hormone frequently associated with increased tumor invasiveness, including in TNBC. Here, to overcome the immune-suppressive environment within TNBC tumors to enable more effective cancer therapy, we engineered a bispecific antibody (bsAb) targeting both Siglec15 and TGF-β. In mice engrafted with orthotopic 4T1 tumors, S

SUBMITTER: Shen L 

PROVIDER: S-EPMC11561775 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature