Cancer Therapy Can Learn from How the Immune System Overcomes Bacterial Inactivation of Host Antibodies
The Bacterial IdeS Protease as a Strategy for Tumor Regression
Publications
Schmidt A, DeRiggi D, Jordan RE, Whitaker B, Heavner GA, Kruszynski M. A Synthetic Peptide Approach for Elucidating the Points of Natural Auto-Antibody Reactivity to Proteolytic Fragments of Human IgG. Peptide Science, 88:556-557, 2007.
Ryan MH, DeRiggi D, Nemeth JM, Barnathan E, Bjorck L, Jordan RE. Proteolysis of monoclonal IgGs by human and bacterial enzymes in vitro and the detection of proteolytic fragments of endogenous IgG in rheumatoid synovial fluid. Mol. Immunol. 45: 1837-1846, 2008.
Brezski RJ, Luongo JL, Petrone D, Ryan MH, Zhong D, Tam SH, Schmidt AS, Kruszynski M, Whitaker BP, Knight DM, Jordan RE. Human Anti-IgG1 HingeAutoantibodies Reconstitute the Effector Functions of Proteolytically Inactivated IgGs. J.Immunology, 181: 3183-3192, 2008.
Brezski RJ, Vafa O, Petrone D, Tam SH, Powers G, Ryan MH, Luongo JL, Oberholtzer A, Knight DM, and Jordan RE. Tumor-associated and microbial proteases compromise host IgG effector functions by a single cleavage proximal to the hinge. PNAS, 106: 17864-17869, 2009
Brezski RJ and Jordan RE. Cleavage of IgGs by proteases associated with invasive diseases: An evasion tactic against host immunity? mAbs, 2: 1-9, 2010.
Brezski RJ, Knight DM and Jordan RE. The Origins, Specificity, and Potential Biological Relevance of Human Anti-IgG1 Hinge Autoantibodies. TheScientificWorld Journal (TSW), 11: 1153-1167, 2011.
Brezski RJ, Oberholtzer A, Strake B, Jordan RE. The in vitro resistance of IgG2 to proteolytic attack concurs with a comparative paucity of autoantibodies against peptide analogs of the IgG2 hinge. mAbs, Q4, 3: 558-567, 2011.
Grugan KD, McCabe FL, Kinder M, Oberholtzer A, Harman BC, Ekert JE, van Rooijen N, Anderson MA, Nemeth JA, Strohl WR, Jordan RE, Brezski RJ. Tumor-associated macrophages promote invasion while retaining Fc-dependent anti-tumor function. J. Immunology, 189: 5457-5466, 2012
Fan X, Brezski RJ, Fa M, Deng F, Oberholtzer A, Gonzalez A, Dubinsky WP, Strohl WR, Jordan RE, Zhang N and An Z. A single proteolytic cleavage within the lower hinge of trastuzumab reduces immune effector function and in vivo efficacy. Breast Cancer Research, 14:R116, 2012
Kinder M, Greenplate AR, Grugan KD, Soring K, Heeringa KA, McCarthy SD, Bannish G, Perpetua M, Lynch F, Jordan RE, Strohl WR, Brezski RJ. Engineered protease-resistant Abs with selectable cell-killing functions. J. Biol. Chem. 288: 30843-54, 2013.
Jordan RE, Tam SH, Nedelman MA. The bacterial IdeS protease as a strategy for tumor regression. Presented at the 2024 Soc. For Immunotherapy in Cancer annual meeting, Houston TX
Jordan RE, Tam SH, Nedelman MA. Cancer Therapy can learn from How the Immune System Overcomes Bacterial Inactivation of Host Antibodies. Presented at the 2025 Soc. For Immunotherapy in Cancer annual meeting, Washington DC
Malia TJ, Teplyakov A, Brezski RJ, Luo J, Kinder M, Sweet RW, Almagro JC, Jordan RE, Gilliland GL. Structure and Specificity of an Antibody Targeting a Proteolytically-cleaved IgG Hinge. PROTEINS: Structure, Function, andBioinformatics, 82: 1656-1667, 2014.
Brezski RJ, Kinder M, Grugan KD, Soring KL, Carton J, Greenplate AR, Petley T, Makropoulos D, Brosnan K, Emmell E, Watson S, Jordan RE. A monoclonal antibody against hinge-cleaved IgG restores effector function to proteolytically inactivated IgGs in vitro and in vivo. mAbs, 6:5, 1-9; 2014.
Kinder M, Greenplate AR, Strohl WR, Jordan RE, Brezski RJ. An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions. mAbs, 7:3, 494-504; 2015
Shi Y, Fan X, Deng H, Brezski RJ, Rycyzyn M, Jordan RE, Strohl WR, Zou Q, Zhang N and An Z. Trastuzumab triggers phagocytic killing of high HER2 cancer cells by interaction with FcγRIV on immune cells. J Immunol. 194:4379-86, 2015
Fan X, Brezski RJ, Deng H, Dhupkar P, Shi Y, Gonzalez A, Zhang S, Rycyzyn M, Strohl WR, Jordan RE, Zhang N, An Z. A novel therapeutic strategy to rescue the immune effector function of proteolytically inactivated cancer therapeutic antibodies. Molecular Cancer Therapeutics. 14: 681-91; 2015.
Zhang N, Deng H, Fan X, Gonzalez A, Zhang S, Brezski RJ, Choi B-K, Rycyzyn M, Strohl WS, Jordan RE, and An Z. Dysfunctional antibodies in the tumor microenvironment associate with impaired anticancer immunity. Clinical Cancer Research, 21: 5380-5390; 2015
Zhang N, Jordan RE, An Z. Authors’ view: tumor evasion of humoral immunity mediated by proteolytic impairment of antibody triggered immune effector function. An invited review of the paper in Clinical Cancer Research. Oncoimmunology, Vol 5, No 5 e1122861, 2016.
Jordan RE, Fernandez J, Brezski RJ, Greenplate AR, Knight DM, Raju TS, Lynch AS. A peptide immunization approach to counteract a Staphylococcus aureus protease defense against host immunity. Immunology Letters. 172: 29-39; 2016.
Hsiao H-C, Fan WX, Salazar GT, Jordan RE, Zhang N, and An Z. Proteolytic single hinge cleavage of pertuzumab impairs its FC effector function and antitumor activity in vitro and in vivo. Breast Cancer Research, 20:43, 2018
Jordan RE, Fan X, Salazar GT, Zhang N, and An Z. Proteinase-nicked IgGs: an unanticipated target for tumor immunotherapy, Oncoimmunology, 7; e1480300, 2018
Fan X, Yuan Z, Zhao Y, Xion W, Hsiao H-C, Rahnawati P, Ding J, Almosa A, Sun K, Zhang S, Jordan RE, Lee CS, An Z, Zhang N. Impairment of IgG Fc function promotes tumor progression and suppresses NK cell antitumor actions. Nature communications biology. 5, 960, doi.org/10.1038/s42003-022-03931-7 , 2022