Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement

Rony Dahan ¹, Bryan C Barnhart ², Fubin Li ¹, Aaron P Yamniuk ³, Alan J Korman ², Jeffrey V Ravetch ⁴

Affiliations

¹ Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA.
² Bristol-Myers Squibb, Biologics Discovery California, 700 Bay Road, Redwood City, CA 94063, USA.
³ Bristol-Myers Squibb, Department of Molecular Discovery Technologies, Princeton, NJ 08543, USA.
⁴ Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA. Electronic address: ravetch@rockefeller.edu.

PMID: 27265505
38 References
65 citations

Abstract

While engagement of the inhibitory Fcγ-receptor (FcγR) IIB is an absolute requirement for in vivo antitumor activity of agonistic mouse anti-CD40 monoclonal antibodies (mAbs), a similar requirement for human mAbs has been disputed. By using a mouse model humanized for its FcγRs and CD40, we revealed that FcγRIIB engagement is essential for the activity of human CD40 mAbs, while engagement of the activating FcγRIIA inhibits this activity. By engineering Fc variants with selective enhanced binding to FcγRIIB, but not to FcγRIIA, significantly improved antitumor immunity was observed. These findings highlight the necessity of optimizing the Fc domain for this class of therapeutic antibodies by using appropriate preclinical models that accurately reflect the unique affinities and cellular expression of human FcγR.

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References
Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. T Meyer, L Robles-Carrillo, +6 authors, A Amirkhosravi. less J Thromb Haemost, 2008 Nov 06; 7(1). PMID: 18983497
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman. less Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248 Highly Cited.
Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Falk Nimmerjahn, Jeffrey V Ravetch. Science, 2005 Dec 03; 310(5753). PMID: 16322460 Highly Cited.
Antitumor activities of agonistic anti-TNFR antibodies require differential FcγRIIB coengagement in vivo. Fubin Li, Jeffrey V Ravetch. Proc Natl Acad Sci U S A, 2013 Nov 13; 110(48). PMID: 24218606 Free PMC article.
Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. Robert H Vonderheide, Keith T Flaherty, +12 authors, Scott J Antonia. less J Clin Oncol, 2007 Mar 01; 25(7). PMID: 17327609 Highly Cited.
Immunostimulatory monoclonal antibodies for cancer therapy. Ignacio Melero, Sandra Hervas-Stubbs, +2 authors, Martin Glennie, Drew M Pardoll, Lieping Chen. less Nat Rev Cancer, 2007 Jan 26; 7(2). PMID: 17251916 Highly Cited. Review.
Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect. David J DiLillo, Jeffrey V Ravetch. Cell, 2015 May 16; 161(5). PMID: 25976835 Free PMC article. Highly Cited.
FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. Rony Dahan, Emanuela Sega, +3 authors, Jeffrey V Ravetch. less Cancer Cell, 2015 Sep 17; 28(3). PMID: 26373277 Highly Cited.
Ex vivo assays of dendritic cell activation and cytokine profiles as predictors of in vivo effects in an anti-human CD40 monoclonal antibody ChiLob 7/4 phase I trial. F Chowdhury, P W Johnson, M J Glennie, A P Williams. Cancer Immunol Res, 2014 Apr 30; 2(3). PMID: 24778319 Free PMC article.
A bacterial artificial chromosome library for sequencing the complete human genome. K Osoegawa, A G Mammoser, +4 authors, P J de Jong. less Genome Res, 2001 Mar 07; 11(3). PMID: 11230172 Free PMC article.
Mouse model recapitulating human Fcγ receptor structural and functional diversity. Patrick Smith, David J DiLillo, +2 authors, Stylianos Bournazos, Fubin Li, Jeffrey V Ravetch. less Proc Natl Acad Sci U S A, 2012 Apr 05; 109(16). PMID: 22474370 Free PMC article. Highly Cited.
A general requirement for FcγRIIB co-engagement of agonistic anti-TNFR antibodies. Fubin Li, Jeffrey V Ravetch. Cell Cycle, 2012 Aug 25; 11(18). PMID: 22918247 Free PMC article.
Immune activation and a 9-year ongoing complete remission following CD40 antibody therapy and metastasectomy in a patient with metastatic melanoma. David L Bajor, Xiaowei Xu, +8 authors, Robert H Vonderheide. less Cancer Immunol Res, 2014 Sep 26; 2(11). PMID: 25252722 Free PMC article.
Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice. Liza Robles-Carrillo, Todd Meyer, +8 authors, Ali Amirkhosravi. less J Immunol, 2010 Jun 30; 185(3). PMID: 20585032
Interaction with FcγRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. Ann L White, H T Claude Chan, +10 authors, Martin J Glennie. less J Immunol, 2011 Jul 12; 187(4). PMID: 21742972
Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Pierre Bruhns, Bruno Iannascoli, +4 authors, Marc Daëron. less Blood, 2008 Nov 20; 113(16). PMID: 19018092 Highly Cited.
Interchain disulfide bonding in human IgG2 antibodies probed by site-directed mutagenesis. Martin J Allen, Amy Guo, +8 authors, Alain Balland. less Biochemistry, 2009 Mar 04; 48(17). PMID: 19254029
Tracking CD40 signaling during germinal center development. Katia Basso, Ulf Klein, +5 authors, Riccardo Dalla-Favera. less Blood, 2004 Aug 28; 104(13). PMID: 15331443
A phase I study of dacetuzumab (SGN-40, a humanized anti-CD40 monoclonal antibody) in patients with chronic lymphocytic leukemia. Richard R Furman, Andres Forero-Torres, Andrei Shustov, Jonathan G Drachman. Leuk Lymphoma, 2009 Dec 30; 51(2). PMID: 20038235
Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Jens Rüter, Scott J Antonia, +2 authors, Howard A Burris, Richard D Huhn, Robert H Vonderheide. less Cancer Biol Ther, 2010 Sep 22; 10(10). PMID: 20855968 Free PMC article.
Pathways Responsible for Human Autoantibody and Therapeutic Intravenous IgG Activity in Humanized Mice. Inessa Schwab, Anja Lux, Falk Nimmerjahn. Cell Rep, 2015 Oct 13; 13(3). PMID: 26456831
CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. David P Inwald, Alison McDowall, +2 authors, Mark J Peters, Robin E Callard, Nigel J Klein. less Circ Res, 2003 Apr 05; 92(9). PMID: 12676820
Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Fubin Li, Jeffrey V Ravetch. Science, 2011 Aug 20; 333(6045). PMID: 21852502 Free PMC article. Highly Cited.
Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Stylianos Bournazos, Florian Klein, +3 authors, Jeffrey V Ravetch. less Cell, 2014 Sep 13; 158(6). PMID: 25215485 Free PMC article. Highly Cited.
Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Seung Y Chu, Igor Vostiar, +6 authors, John R Desjarlais. less Mol Immunol, 2008 Aug 12; 45(15). PMID: 18691763
FcgammaRI-deficient mice show multiple alterations to inflammatory and immune responses. Nadine Barnes, Amanda L Gavin, +3 authors, P Mark Hogarth. less Immunity, 2002 Mar 26; 16(3). PMID: 11911823
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982 Free PMC article. Highly Cited.
Type I and type II Fc receptors regulate innate and adaptive immunity. Andrew Pincetic, Stylianos Bournazos, +5 authors, Jeffrey V Ravetch. less Nat Immunol, 2014 Jul 22; 15(8). PMID: 25045879 Free PMC article. Highly Cited. Review.
OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy. Yannick Bulliard, Rose Jolicoeur, +3 authors, Jennifer L Brogdon. less Immunol Cell Biol, 2014 Apr 16; 92(6). PMID: 24732076 Highly Cited.
FcgammaR polymorphisms: Implications for function, disease susceptibility and immunotherapy. N M van Sorge, W-L van der Pol, J G J van de Winkel. Tissue Antigens, 2003 Apr 16; 61(3). PMID: 12694568 Review.
Role of crosslinking for agonistic CD40 monoclonal antibodies as immune therapy of cancer. Lee P Richman, Robert H Vonderheide. Cancer Immunol Res, 2014 Jan 15; 2(1). PMID: 24416732 Free PMC article.
Conformation of the human immunoglobulin G2 hinge imparts superagonistic properties to immunostimulatory anticancer antibodies. Ann L White, H T Claude Chan, +15 authors, Martin J Glennie. less Cancer Cell, 2014 Dec 17; 27(1). PMID: 25500122 Free PMC article.
Agonistic CD40 antibodies and cancer therapy. Robert H Vonderheide, Martin J Glennie. Clin Cancer Res, 2013 Mar 06; 19(5). PMID: 23460534 Free PMC article. Highly Cited.
Engineered antibody Fc variant with selectively enhanced FcγRIIb binding over both FcγRIIa(R131) and FcγRIIa(H131). F Mimoto, H Katada, +7 authors, K Hattori. less Protein Eng Des Sel, 2013 Jun 08; 26(10). PMID: 23744091 Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981 Free PMC article. Highly Cited.
FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Falk Nimmerjahn, Pierre Bruhns, Ken Horiuchi, Jeffrey V Ravetch. Immunity, 2005 Jul 26; 23(1). PMID: 16039578 Highly Cited.
Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Robert H Vonderheide, Jennifer M Burg, +5 authors, Omid Hamid. less Oncoimmunology, 2013 Mar 14; 2(1). PMID: 23483678 Free PMC article.
Fcgamma receptors as regulators of immune responses. Falk Nimmerjahn, Jeffrey V Ravetch. Nat Rev Immunol, 2007 Dec 08; 8(1). PMID: 18064051 Highly Cited. Review.

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CIMT 2016: Mechanisms of efficacy in cancer immunotherapy - Report on the 14th Annual Meeting of the Association for Cancer Immunotherapy May 10-12 2016, Mainz, Germany. Lena M Kranz, Matthias Birtel, +7 authors, Mustafa Diken. less Hum Vaccin Immunother, 2016 Jul 21; 12(11). PMID: 27435168 Free PMC article.
Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists. Gregory L Beatty, Yan Li, Kristen B Long. Expert Rev Anticancer Ther, 2016 Dec 09; 17(2). PMID: 27927088 Free PMC article. Review.
Role of Fc-FcγR interactions in the antitumor activity of therapeutic antibodies. Bryan C Barnhart, Michael Quigley. Immunol Cell Biol, 2016 Dec 16; 95(4). PMID: 27974746 Review.
Signaling by Antibodies: Recent Progress. Stylianos Bournazos, Taia T Wang, +2 authors, Rony Dahan, Jad Maamary, Jeffrey V Ravetch. less Annu Rev Immunol, 2017 Apr 28; 35. PMID: 28446061 Free PMC article. Highly Cited. Review.
Quantitative Mass Spectrometry Analysis of PD-L1 Protein Expression, N-glycosylation and Expression Stoichiometry with PD-1 and PD-L2 in Human Melanoma. Carlos A Morales-Betanzos, Hyoungjoo Lee, +4 authors, Daniel C Liebler. less Mol Cell Proteomics, 2017 May 27; 16(10). PMID: 28546465 Free PMC article.
TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines. Timothy Nj Bullock. Curr Opin Immunol, 2017 Jul 28; 47. PMID: 28750279 Free PMC article. Review.
Safety, pharmacokinetics, and pharmacodynamics of oral omaveloxolone (RTA 408), a synthetic triterpenoid, in a first-in-human trial of patients with advanced solid tumors. Ben C Creelan, Dmitry I Gabrilovich, +12 authors, Scott J Antonia. less Onco Targets Ther, 2017 Sep 19; 10. PMID: 28919776 Free PMC article.
Next generation antibody drugs: pursuit of the 'high-hanging fruit'. Paul J Carter, Greg A Lazar. Nat Rev Drug Discov, 2017 Dec 02; 17(3). PMID: 29192287 Highly Cited. Review.
Trial Watch: Immunostimulatory monoclonal antibodies for oncological indications. Mariona Cabo, Rienk Offringa, +3 authors, Lorenzo Galluzzi. less Oncoimmunology, 2017 Dec 07; 6(12). PMID: 29209572 Free PMC article. Review.
FcγRII-binding Centyrins mediate agonism and antibody-dependent cellular phagocytosis when fused to an anti-OX40 antibody. Di Zhang, Brian Whitaker, Mehabaw G Derebe, Mark L Chiu. MAbs, 2018 Jan 24; 10(3). PMID: 29359992 Free PMC article.
Cancer Immunotherapy: Factors Important for the Evaluation of Safety in Nonclinical Studies. Danuta J Herzyk, Helen G Haggerty. AAPS J, 2018 Feb 09; 20(2). PMID: 29417397 Review.
Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity. Sabine Hoves, Chia-Huey Ooi, +15 authors, Carola H Ries. less J Exp Med, 2018 Feb 14; 215(3). PMID: 29436396 Free PMC article. Highly Cited.
Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448. Simeon Cua, Heng Liang Tan, +6 authors, Andre Choo. less Oncotarget, 2018 Mar 24; 9(17). PMID: 29568351 Free PMC article.
Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies. Xiaojie Yu, H T Claude Chan, +14 authors, Ann L White. less Cancer Cell, 2018 Mar 27; 33(4). PMID: 29576376 Free PMC article.
The Immune Revolution: A Case for Priming, Not Checkpoint. Robert H Vonderheide. Cancer Cell, 2018 Apr 11; 33(4). PMID: 29634944 Free PMC article. Highly Cited. Review.
Bispecific antibodies in cancer immunotherapy. Eva Dahlén, Niina Veitonmäki, Per Norlén. Ther Adv Vaccines Immunother, 2018 Jul 13; 6(1). PMID: 29998217 Free PMC article. Highly Cited. Review.
Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. David A Knorr, Rony Dahan, Jeffrey V Ravetch. Proc Natl Acad Sci U S A, 2018 Oct 10; 115(43). PMID: 30297432 Free PMC article.
Immune Checkpoints as Therapeutic Targets in Autoimmunity. Christopher Paluch, Ana Mafalda Santos, +2 authors, Simon J Davis. less Front Immunol, 2018 Oct 24; 9. PMID: 30349540 Free PMC article. Review.
IL-15 enhanced antibody-dependent cellular cytotoxicity mediated by NK cells and macrophages. Meili Zhang, Bernard Wen, +8 authors, Thomas A Waldmann. less Proc Natl Acad Sci U S A, 2018 Oct 31; 115(46). PMID: 30373815 Free PMC article.
The pharmacology and therapeutic applications of monoclonal antibodies. María Sofía Castelli, Paul McGonigle, Pamela J Hornby. Pharmacol Res Perspect, 2019 Dec 21; 7(6). PMID: 31859459 Free PMC article. Review.
Myeloid immunosuppression and immune checkpoints in the tumor microenvironment. Kyohei Nakamura, Mark J Smyth. Cell Mol Immunol, 2019 Oct 16; 17(1). PMID: 31611651 Free PMC article. Highly Cited. Review.
Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer. Thomas A Waldmann, Milos D Miljkovic, Kevin C Conlon. J Exp Med, 2019 Dec 11; 217(1). PMID: 31821442 Free PMC article. Review.
Characterization of Mauritian Cynomolgus Macaque FcγR Alleles Using Long-Read Sequencing. Amelia K Haj, Jaren M Arbanas, +13 authors, David H O'Connor. less J Immunol, 2018 Dec 12; 202(1). PMID: 30530595 Free PMC article.
Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity. Xinyue Qi, Fanlin Li, +4 authors, Xuanming Yang. less Nat Commun, 2019 May 21; 10(1). PMID: 31105267 Free PMC article.
CD137 promotes bone metastasis of breast cancer by enhancing the migration and osteoclast differentiation of monocytes/macrophages. Pengling Jiang, Wenjuan Gao, +10 authors, Na Li. less Theranostics, 2019 Jun 28; 9(10). PMID: 31244935 Free PMC article.
Human immunoglobulin G hinge regulates agonistic anti-CD40 immunostimulatory and antitumour activities through biophysical flexibility. Xiaobo Liu, Yingjie Zhao, +8 authors, Fubin Li. less Nat Commun, 2019 Sep 29; 10(1). PMID: 31562320 Free PMC article.
Concepts for agonistic targeting of CD40 in immuno-oncology. David M Richards, Julian P Sefrin, +2 authors, Christian Gieffers, Oliver Hill, Christian Merz. less Hum Vaccin Immunother, 2019 Aug 14; 16(2). PMID: 31403344 Free PMC article. Review.
Impact of Human FcγR Gene Polymorphisms on IgG-Triggered Cytokine Release: Critical Importance of Cell Assay Format. Khiyam Hussain, Chantal E Hargreaves, +9 authors, Mark S Cragg. less Front Immunol, 2019 Mar 23; 10. PMID: 30899264 Free PMC article.
Targeted APC Activation in Cancer Immunotherapy to Enhance the Abscopal Effect. Nathan Suek, Luis Felipe Campesato, Taha Merghoub, Danny N Khalil. Front Immunol, 2019 Apr 20; 10. PMID: 31001249 Free PMC article. Review.
Differentiated agonistic antibody targeting CD137 eradicates large tumors without hepatotoxicity. Ugur Eskiocak, Wilson Guzman, +21 authors, Robert Tighe. less JCI Insight, 2020 Mar 13; 5(5). PMID: 32161196 Free PMC article.
Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB. Ingrid Teige, Linda Mårtensson, Björn L Frendéus. Front Immunol, 2019 Apr 02; 10. PMID: 30930905 Free PMC article. Review.
How to select IgG subclasses in developing anti-tumor therapeutic antibodies. Jifeng Yu, Yongping Song, Wenzhi Tian. J Hematol Oncol, 2020 May 07; 13(1). PMID: 32370812 Free PMC article. Review.
Antibodies targeting sialyl Lewis A mediate tumor clearance through distinct effector pathways. Polina Weitzenfeld, Stylianos Bournazos, Jeffrey V Ravetch. J Clin Invest, 2019 Aug 20; 129(9). PMID: 31424423 Free PMC article.
IL-15 in the Combination Immunotherapy of Cancer. Thomas A Waldmann, Sigrid Dubois, Milos D Miljkovic, Kevin C Conlon. Front Immunol, 2020 Jun 09; 11. PMID: 32508818 Free PMC article. Review.
Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity. Xiaojie Yu, H T Claude Chan, +13 authors, Mark S Cragg. less Cancer Cell, 2020 May 23; 37(6). PMID: 32442402 Free PMC article.
FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells. Lucia Campos Carrascosa, Adriaan A van Beek, +19 authors, Jaap Kwekkeboom. less J Immunother Cancer, 2020 Sep 10; 8(2). PMID: 32900860 Free PMC article.
ICOS agonism by JTX-2011 (vopratelimab) requires initial T cell priming and Fc cross-linking for optimal T cell activation and anti-tumor immunity in preclinical models. Amanda Hanson, Kutlu Elpek, +16 authors, Christopher J Harvey. less PLoS One, 2020 Sep 25; 15(9). PMID: 32970735 Free PMC article.
CD40- and CD95-specific antibody single chain-Baff fusion proteins display BaffR-, TACI- and BCMA-restricted agonism. Johannes Nelke, Juliane Medler, +2 authors, Harald Wajant. less MAbs, 2020 Aug 26; 12(1). PMID: 32840410 Free PMC article.
Improved Detection of in vivo Human NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Using a Novel NOG-FcγR-Deficient Human IL-15 Transgenic Mouse. Ikumi Katano, Ryoji Ito, Kenji Kawai, Takeshi Takahashi. Front Immunol, 2020 Oct 30; 11. PMID: 33117338 Free PMC article.
Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection. Stylianos Bournazos, Davide Corti, Herbert W Virgin, Jeffrey V Ravetch. Nature, 2020 Oct 09; 588(7838). PMID: 33032297 Free PMC article.
Concomitant or delayed anti-TNF differentially impact on immune-related adverse events and antitumor efficacy after anti-CD40 therapy. Celia Jacoberger-Foissac, Stephen J Blake, +5 authors, Michele Wl Teng. less J Immunother Cancer, 2020 Nov 18; 8(2). PMID: 33199513 Free PMC article.
New emerging targets in cancer immunotherapy: the role of Cluster of Differentiation 40 (CD40/TNFR5). Manuel Piechutta, Anna Sophie Berghoff. ESMO Open, 2019 Jul 06; 4(Suppl 3). PMID: 31275618 Free PMC article. Review.
Fc-Engineering for Modulated Effector Functions-Improving Antibodies for Cancer Treatment. Rena Liu, Robert J Oldham, +2 authors, Emma Teal, Stephen A Beers, Mark S Cragg. less Antibodies (Basel), 2020 Nov 21; 9(4). PMID: 33212886 Free PMC article. Review.
Fusion of Bacterial Flagellin to a Dendritic Cell-Targeting αCD40 Antibody Construct Coupled With Viral or Leukemia-Specific Antigens Enhances Dendritic Cell Maturation and Activates Peptide-Responsive T Cells. Saskia Schmitt, Siret Tahk, +12 authors, Marion Subklewe. less Front Immunol, 2020 Dec 08; 11. PMID: 33281829 Free PMC article.
Targeting a scavenger receptor on tumor-associated macrophages activates tumor cell killing by natural killer cells. Silke Eisinger, Dhifaf Sarhan, +17 authors, Mikael C I Karlsson. less Proc Natl Acad Sci U S A, 2020 Nov 25; 117(50). PMID: 33229588 Free PMC article.
APX005M, a CD40 agonist antibody with unique epitope specificity and Fc receptor binding profile for optimal therapeutic application. Erin L Filbert, Pia K Björck, +2 authors, Minu K Srivastava, Frances R Bahjat, Xiaodong Yang. less Cancer Immunol Immunother, 2021 Jan 05; 70(7). PMID: 33392713 Free PMC article.
The Current Landscape of Antibody-based Therapies in Solid Malignancies. Ashu Shah, Sanchita Rauth, +6 authors, Surinder K Batra. less Theranostics, 2021 Jan 05; 11(3). PMID: 33391547 Free PMC article. Review.
Harnessing innate immunity in cancer therapy. Olivier Demaria, Stéphanie Cornen, +3 authors, Eric Vivier. less Nature, 2019 Oct 04; 574(7776). PMID: 31578484 Highly Cited. Review.
A general Fc engineering platform for the next generation of antibody therapeutics. Da Chen, Yingjie Zhao, +21 authors, Hongkai Zhang. less Theranostics, 2021 Jan 08; 11(4). PMID: 33408788 Free PMC article.
Domain binding and isotype dictate the activity of anti-human OX40 antibodies. Jordana Griffiths, Khiyam Hussain, +18 authors, Mark S Cragg. less J Immunother Cancer, 2021 Jan 12; 8(2). PMID: 33428585 Free PMC article.
Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint. TingTing Tang, Xiang Cheng, +3 authors, Hong Wang. less Pharmacol Ther, 2020 Oct 23; 219. PMID: 33091428 Free PMC article. Review.
Isotype selection for antibody-based cancer therapy. N Vukovic, A van Elsas, J S Verbeek, D M W Zaiss. Clin Exp Immunol, 2020 Nov 07; 203(3). PMID: 33155272 Free PMC article. Review.
Receptor Oligomerization and Its Relevance for Signaling by Receptors of the Tumor Necrosis Factor Receptor Superfamily. Kirstin Kucka, Harald Wajant. Front Cell Dev Biol, 2021 Mar 02; 8. PMID: 33644033 Free PMC article. Review.
Agonistic CD40 Antibodies in Cancer Treatment. Dijana Djureinovic, Meina Wang, Harriet M Kluger. Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33804039 Free PMC article. Review.
Inhibition of the Adenosine Pathway to Potentiate Cancer Immunotherapy: Potential for Combinatorial Approaches. Elizabeth A Thompson, Jonathan D Powell. Annu Rev Med, 2020 Sep 10; 72. PMID: 32903139 Free PMC article. Review.
Co-Stimulatory versus Cell Death Aspects of Agonistic CD40 Monoclonal Antibody Selicrelumab in Chronic Lymphocytic Leukemia. Raquel Delgado, Karoline Kielbassa, +5 authors, Eric Eldering. less Cancers (Basel), 2021 Jul 03; 13(12). PMID: 34205588 Free PMC article.
Development of Therapeutic Antibodies and Modulating the Characteristics of Therapeutic Antibodies to Maximize the Therapeutic Efficacy. Seung Hyun Kang, Chang-Han Lee. Biotechnol Bioprocess Eng, 2021 Jul 06; 26(3). PMID: 34220207 Free PMC article. Review.
Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer. Christopher S Garris, Jeffrey L Wong, Jeffrey V Ravetch, David A Knorr. Sci Transl Med, 2021 May 21; 13(594). PMID: 34011627 Free PMC article.
Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties. Valentina Ceglia, Sandra Zurawski, +6 authors, Gerard Zurawski. less J Immunol, 2021 Sep 24; 207(8). PMID: 34551965 Free PMC article.
Agonist antibody discovery: Experimental, computational, and rational engineering approaches. John S Schardt, Harkamal S Jhajj, +3 authors, Peter M Tessier. less Drug Discov Today, 2021 Sep 28; 27(1). PMID: 34571277 Free PMC article. Review.
Anti-CD40 Antibody Fused to CD40 Ligand Is a Superagonist Platform for Adjuvant Intrinsic DC-Targeting Vaccines. Valentina Ceglia, Sandra Zurawski, +7 authors, Gerard Zurawski. less Front Immunol, 2022 Feb 01; 12. PMID: 35095862 Free PMC article.
Agonistic CD27 antibody potency is determined by epitope-dependent receptor clustering augmented through Fc-engineering. Franziska Heckel, Anna H Turaj, +12 authors, Sean H Lim. less Commun Biol, 2022 Mar 16; 5(1). PMID: 35288635 Free PMC article.
Clinical relevance of tumour-associated macrophages. Mikael J Pittet, Olivier Michielin, Denis Migliorini. Nat Rev Clin Oncol, 2022 Apr 01; 19(6). PMID: 35354979 Review.
The tumor-targeted CD40 agonist CEA-CD40 promotes T cell priming via a dual mode of action by increasing antigen delivery to dendritic cells and enhancing their activation. Eva Sum, Moritz Rapp, +4 authors, Pablo Umaña. less J Immunother Cancer, 2022 Mar 17; 10(3). PMID: 35292514 Free PMC article.
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