Background: Hu5F9-G4, a human immunoglobulin G4 (IgG4) monoclonal antibody
(mAb) has recently been granted fast-track designation by the FDA for the treatment
of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular
lymphoma. Hu5F9-G4 has the ability to block CD47-SIRPα signaling along with anti-
EGFR and anti-PD-L1 immune checkpoint activity that is involved in a variety of cancers
like solid tumors, Non-Hodgkin’s Lymphoma (NHL), colorectal cancer (CRC), breast,
ovarian and bladder cancers, and hematological malignancies. Thus, Hu5F9-G4 is an important
biologic that has increasing clinical relevance in cancer care.
Methods: We queried PubMed, Web of Science, Google Scholar, Science Direct and Scopus
databases with keywords pertaining to Hu5F9-G4. In addition, we have included the
Hu5F9-G4 data presented at the 60th American Society of Hematology (ASH) Annual
Meeting, the American Society of Clinical Oncology (ASCO) Annual Meeting and 23rd
Congress of the European Hematology Association (EHA).
Results: We discuss the mechanistic basis and preclinical evidence for the anticancer activity
of Hu5F9-G4. Further, we delineate clinical studies, alone and in combination with
anti-CD20 mAb rituximab, anti-EGFR mAb cetuximab, PD-L1 checkpoint inhibitors avelumab
and atezolizumab, and anti-HER2 mAb trastuzumab. Moreover, the potential adverse
effects, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 with emphasis on
the role of CD47-SIRPα signaling in phagocytosis are presented.
Conclusion: Taken together, we review the pharmacokinetics and systems pharmacology
of Hu5F9-G4 which appears to hold great promise for the future of cancer care.