Phosphatidylserine-targeting monoclonal antibodies exhibit distinct biochemical and cellular effects on anti-CD3/ CD28-stimulated T cell IFN-g and TNF-a production

David Calianese, Tamara Kreiss, Canan Kasikara, Viralkumar Davra, Kevin C. Lahey, Varsha Gadiyar, Ke Geng, Sukhwinder Singh, William Honnen, Dabbu Kumar Jaijyan, Charles Reichman, John Siekierka, Maria Laura Gennaro, Sergei V. Kotenko, David S. Ucker, Rolf A. Brekken, Abraham Pinter, Raymond B. Birge, Alok Choudhary

Research output: Contribution to journalArticlepeer-review


Phosphatidylserine (PS)-targeting monoclonal Abs (mAbs) that directly target PS and target PS via b2-gp1 (b2GP1) have been in preclinical and clinical development for over 10 y for the treatment of infectious diseases and cancer. Although the intended targets of PS-binding mAbs have traditionally included pathogens as well as stressed tumor cells and its associated vasculature in oncology, the effects of PS-targeting mAbs on activated immune cells, notably T cells, which externalize PS upon Ag stimulation, is not well understood. Using human T cells from healthy donor PBMCs activated with an anti-CD3 + anti-CD28 Ab mixture (anti-CD3/CD28) as a model for TCR-mediated PS externalization and T cell stimulation, we investigated effects of two different PS-targeting mAbs, 11.31 and bavituximab (Bavi), on TCR activation and TCR-mediated cytokine production in an ex vivo paradigm. Although 11.31 and Bavi bind selectivity to anti-CD3/28 activated T cells in a PS-dependent manner, surprisingly, they display distinct functional activities in their effect on IFN-g and TNF-A production, whereby 11.31, but not Bavi, suppressed cytokine production. This inhibitory effect on anti-CD3/28 activated T cells was observed on both CD4+ and CD8+ cells and independently of monocytes, suggesting the effects of 11.31 were directly mediated by binding to externalized PS on activated T cells. Imaging showed 11.31 and Bavi bind at distinct focal depots on the cell membrane. Collectively, our findings indicate that PS-targeting mAb 11.31 suppresses cytokine production by anti-CD3/28 activated T cells.

Original languageEnglish (US)
Pages (from-to)436-448
Number of pages13
JournalJournal of Immunology
Issue number2
StatePublished - Jul 15 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Phosphatidylserine-targeting monoclonal antibodies exhibit distinct biochemical and cellular effects on anti-CD3/ CD28-stimulated T cell IFN-g and TNF-a production'. Together they form a unique fingerprint.

Cite this