Journal Article
. 2013 Mar; 19(5):1035-43.
doi: 10.1158/1078-0432.CCR-12-2064.

Agonistic CD40 antibodies and cancer therapy

Robert H Vonderheide 1 Martin J Glennie  
Affiliations
  • PMID: 23460534
  •     57 References
  •     201 citations

Abstract

Recent success in cancer immunotherapy has reinvigorated the hypothesis that the immune system can control many if not most cancers, in some cases producing durable responses in a way not seen with many small-molecule drugs. Agonistic CD40 monoclonal antibodies (mAb) offer a new therapeutic option which has the potential to generate anticancer immunity by various mechanisms. CD40 is a TNF receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B cells, and monocytes as well as many nonimmune cells and a range of tumors. Agonistic CD40 mAb have been shown to activate APC and promote antitumor T-cell responses and to foster cytotoxic myeloid cells with the potential to control cancer in the absence of T-cell immunity. Thus, agonistic CD40 mAb are fundamentally different from mAb which block negative immune checkpoint such as anti-CTLA-4 or anti-PD-1. Initial clinical trials of agonistic CD40 mAb have shown highly promising results in the absence of disabling toxicity, both in single-agent studies and in combination with chemotherapy; however, numerous questions remain about dose, schedule, route of administration, and formulation. Recent findings about the role played by the IgG isotype and the Fc gamma receptor (FcγR) in mAb cross-linking, together with insights into mechanisms of action, particularly with regard to the role of myeloid cells, are predicted to help design next-generation CD40 agonistic reagents with greater efficacy. Here, we will review the preclinical and clinical data and discuss the major issues facing the field.

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Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcγR Engagement.
Rony Dahan, Bryan C Barnhart, +3 authors, Jeffrey V Ravetch.
Cancer Cell, 2016 Jun 07; 29(6). PMID: 27265505    Free PMC article.
Highly Cited.
CD40 Stimulation Obviates Innate Sensors and Drives T Cell Immunity in Cancer.
Katelyn T Byrne, Robert H Vonderheide.
Cell Rep, 2016 Jun 14; 15(12). PMID: 27292635    Free PMC article.
Highly Cited.
Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity.
Caroline Baer, Mario Leonardo Squadrito, +7 authors, Michele De Palma.
Nat Cell Biol, 2016 Jun 14; 18(7). PMID: 27295554
Highly Cited.
A current perspective on applications of macrocyclic-peptide-based high-affinity ligands.
Daniël Leenheer, Peter Ten Dijke, Christopher John Hipolito.
Biopolymers, 2016 Jun 30; 106(6). PMID: 27352774    Free PMC article.
Review.
Neoadjuvant therapy for pancreatic cancer: an ongoing debate.
Suzanne Russo, M Wasif Saif.
Therap Adv Gastroenterol, 2016 Jul 02; 9(4). PMID: 27366211    Free PMC article.
Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).
Guoqi Song, Huiyun Ni, +4 authors, William C Cho.
Onco Targets Ther, 2016 Jul 07; 9. PMID: 27382316    Free PMC article.
Sunitinib enhances the antitumor responses of agonistic CD40-antibody by reducing MDSCs and synergistically improving endothelial activation and T-cell recruitment.
Luuk van Hooren, Maria Georganaki, +2 authors, Anna Dimberg.
Oncotarget, 2016 Jul 08; 7(31). PMID: 27385210    Free PMC article.
Regulatory circuits of T cell function in cancer.
Daniel E Speiser, Ping-Chih Ho, Grégory Verdeil.
Nat Rev Immunol, 2016 Aug 17; 16(10). PMID: 27526640
Highly Cited. Review.
Targeting CD73 in the tumor microenvironment with MEDI9447.
Carl M Hay, Erin Sult, +15 authors, Kris F Sachsenmeier.
Oncoimmunology, 2016 Sep 14; 5(8). PMID: 27622077    Free PMC article.
Highly Cited.
Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination.
Anke Redeker, Ramon Arens.
Front Immunol, 2016 Sep 23; 7. PMID: 27656185    Free PMC article.
Review.
Tumor-directed immunotherapy can generate tumor-specific T cell responses through localized co-stimulation.
Peter Ellmark, Sara M Mangsbo, +2 authors, Thomas H Tötterman.
Cancer Immunol Immunother, 2016 Oct 08; 66(1). PMID: 27714433    Free PMC article.
Review.
AFM study shows prominent physical changes in elasticity and pericellular layer in human acute leukemic cells due to inadequate cell-cell communication.
Nataliia V Guz, Sapan J Patel, +2 authors, Igor Sokolov.
Nanotechnology, 2016 Nov 12; 27(49). PMID: 27834315    Free PMC article.
Resistance to anticancer immunity in cancer patients: potential strategies to reverse resistance.
B Bonavida, S Chouaib.
Ann Oncol, 2016 Nov 20; 28(3). PMID: 27864216    Free PMC article.
Review.
Enhancing radiotherapy for lung cancer using immunoadjuvants delivered in situ from new design radiotherapy biomaterials: a preclinical study.
Yao Hao, Sayeda Yasmin-Karim, +3 authors, Wilfred Ngwa.
Phys Med Biol, 2016 Dec 03; 61(24). PMID: 27910826    Free PMC article.
Targeting cancer-related inflammation in the era of immunotherapy.
Kyohei Nakamura, Mark J Smyth.
Immunol Cell Biol, 2016 Dec 22; 95(4). PMID: 27999432
Review.
Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy.
Kristin L Griffiths, Mushtaq Ahmed, +9 authors, Shabaana A Khader.
Nat Commun, 2016 Dec 23; 7. PMID: 28004802    Free PMC article.
Quantitative analysis of cell surface antigen-antibody interaction using Gaussia princeps luciferase antibody fusion proteins.
Juliane Kums, Johannes Nelke, +3 authors, Harald Wajant.
MAbs, 2017 Jan 18; 9(3). PMID: 28095113    Free PMC article.
Differentiated State of Initiating Tumor Cells Is Key to Distinctive Immune Responses Seen in H-RasG12V-Induced Squamous Tumors.
Michael A Podolsky, Jacob T Bailey, +3 authors, Adam B Glick.
Cancer Immunol Res, 2017 Feb 01; 5(3). PMID: 28137717    Free PMC article.
Aptamers for CD Antigens: From Cell Profiling to Activity Modulation.
Amin Nozari, Maxim V Berezovski.
Mol Ther Nucleic Acids, 2017 Mar 23; 6. PMID: 28325295    Free PMC article.
Review.
Progress in tumor-associated macrophage (TAM)-targeted therapeutics.
Chayanon Ngambenjawong, Heather H Gustafson, Suzie H Pun.
Adv Drug Deliv Rev, 2017 Apr 30; 114. PMID: 28449873    Free PMC article.
Highly Cited. Review.
Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and Emerging Therapeutic Options.
Jessica M Moskovitz, Jennifer Moy, Tanguy Y Seiwert, Robert L Ferris.
Oncologist, 2017 May 17; 22(6). PMID: 28507203    Free PMC article.
Review.
Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters.
Alison M McDonnell, Alistair Cook, +2 authors, Anna K Nowak.
BMC Cancer, 2017 Jun 18; 17(1). PMID: 28619093    Free PMC article.
Tumor-Associated Macrophages as Target for Antitumor Therapy.
Katarzyna Sawa-Wejksza, Martyna Kandefer-Szerszeń.
Arch Immunol Ther Exp (Warsz), 2017 Jul 01; 66(2). PMID: 28660349    Free PMC article.
Review.
Metabolism-associated danger signal-induced immune response and reverse immune checkpoint-activated CD40+ monocyte differentiation.
Jin Dai, Pu Fang, +8 authors, Hong Wang.
J Hematol Oncol, 2017 Jul 26; 10(1). PMID: 28738836    Free PMC article.
Review.
CD27-Mediated Regulatory T Cell Depletion and Effector T Cell Costimulation Both Contribute to Antitumor Efficacy.
Anna Wasiuk, James Testa, +9 authors, Li-Zhen He.
J Immunol, 2017 Nov 08; 199(12). PMID: 29109120    Free PMC article.
Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases.
Fredrik N Albach, Frank Wagner, +6 authors, Jürgen Steffgen.
Eur J Clin Pharmacol, 2017 Nov 12; 74(2). PMID: 29127458    Free PMC article.
Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain.
Manisha Singh, Christina Vianden, +15 authors, Willem W Overwijk.
Nat Commun, 2017 Nov 14; 8(1). PMID: 29129918    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.
Oncoimmunology, 2017 Dec 07; 6(12). PMID: 29209572    Free PMC article.
Review.
Towards personalized, tumour-specific, therapeutic vaccines for cancer.
Zhuting Hu, Patrick A Ott, Catherine J Wu.
Nat Rev Immunol, 2017 Dec 12; 18(3). PMID: 29226910    Free PMC article.
Highly Cited. Review.
Emerging trends in the immunotherapy of pancreatic cancer.
Kasturi Banerjee, Sushil Kumar, +10 authors, Maneesh Jain.
Cancer Lett, 2017 Dec 16; 417. PMID: 29242097    Free PMC article.
Review.
Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity.
Yuan Zhang, Na Li, Heikyung Suh, Darrell J Irvine.
Nat Commun, 2018 Jan 04; 9(1). PMID: 29295974    Free PMC article.
Highly Cited.
Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors.
Lindsay K Ward-Kavanagh, Kathleen M Kokolus, +2 authors, Todd D Schell.
Cancer Immunol Immunother, 2018 Jan 15; 67(4). PMID: 29332158    Free PMC article.
Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity.
Sabine Hoves, Chia-Huey Ooi, +15 authors, Carola H Ries.
J Exp Med, 2018 Feb 14; 215(3). PMID: 29436396    Free PMC article.
Highly Cited.
Macrophages and CD8+ T Cells Mediate the Antitumor Efficacy of Combined CD40 Ligation and Imatinib Therapy in Gastrointestinal Stromal Tumors.
Jennifer Q Zhang, Shan Zeng, +13 authors, Ronald P DeMatteo.
Cancer Immunol Res, 2018 Feb 23; 6(4). PMID: 29467128    Free PMC article.
Next generation of immune checkpoint therapy in cancer: new developments and challenges.
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, +3 authors, Yanyan Lou.
J Hematol Oncol, 2018 Mar 17; 11(1). PMID: 29544515    Free PMC article.
Highly Cited. Review.
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.
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.
Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.
Damir Bojadzic, Peter Buchwald.
Curr Top Med Chem, 2018 Jun 01; 18(8). PMID: 29848279    Free PMC article.
Review.
Immunotherapy and Prevention of Pancreatic Cancer.
Alexander H Morrison, Katelyn T Byrne, Robert H Vonderheide.
Trends Cancer, 2018 Jun 05; 4(6). PMID: 29860986    Free PMC article.
Review.
Selective FcγR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens.
Jeremy D Waight, Dhan Chand, +14 authors, Nicholas S Wilson.
Cancer Cell, 2018 Jun 13; 33(6). PMID: 29894690    Free PMC article.
The promise and challenges of immune agonist antibody development in cancer.
Patrick A Mayes, Kenneth W Hance, Axel Hoos.
Nat Rev Drug Discov, 2018 Jun 16; 17(7). PMID: 29904196
Highly Cited. Review.
Next generation immune-checkpoints for cancer therapy.
Chiara Donini, Lorenzo D'Ambrosio, +2 authors, Dario Sangiolo.
J Thorac Dis, 2018 Jun 29; 10(Suppl 13). PMID: 29951308    Free PMC article.
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.
Emerging strategies for combination checkpoint modulators in cancer immunotherapy.
Aleksandra Popovic, Elizabeth M Jaffee, Neeha Zaidi.
J Clin Invest, 2018 Aug 02; 128(8). PMID: 30067248    Free PMC article.
Highly Cited. Review.
Oncolytic virus and PD-1/PD-L1 blockade combination therapy.
Chun-Yu Chen, Brian Hutzen, Mary F Wedekind, Timothy P Cripe.
Oncolytic Virother, 2018 Aug 15; 7. PMID: 30105219    Free PMC article.
Review.
Abscopal effect of radiotherapy combined with immune checkpoint inhibitors.
Yang Liu, Yinping Dong, +3 authors, Jinming Yu.
J Hematol Oncol, 2018 Aug 18; 11(1). PMID: 30115069    Free PMC article.
Highly Cited. Review.
Personalized cancer neoantigen vaccines come of age.
Yanhong Chu, Qin Liu, Jia Wei, Baorui Liu.
Theranostics, 2018 Aug 22; 8(15). PMID: 30128050    Free PMC article.
Review.
Immunotherapy of hepatocellular carcinoma.
Bruno Sangro, Daniel Palmer, Ignacio Melero.
Hepat Oncol, 2014 Oct 01; 1(4). PMID: 30190978    Free PMC article.
Review.
Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma.
David L Bajor, Rosemarie Mick, +15 authors, Robert H Vonderheide.
Oncoimmunology, 2018 Oct 06; 7(10). PMID: 30288340    Free PMC article.
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 regulation of metastasis: mechanistic insights and therapeutic opportunities.
Olga S Blomberg, Lorenzo Spagnuolo, Karin E de Visser.
Dis Model Mech, 2018 Oct 26; 11(10). PMID: 30355585    Free PMC article.
Review.
Efficacy of different hemodialysis methods on dendritic cell marker CD40 and CD80 and platelet activation marker CD62P and P10 in patients with chronic renal failure.
Xin-Fang Wang, Bei-Hao Zhang, Xiao-Qing Lu, Pei Wang.
J Clin Lab Anal, 2018 Dec 01; 33(3). PMID: 30499177    Free PMC article.
Considerations for the Design of Antibody-Based Therapeutics.
Dennis R Goulet, William M Atkins.
J Pharm Sci, 2019 Jun 08; 109(1). PMID: 31173761    Free PMC article.
Review.
Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies.
José Medina-Echeverz, Maria Hinterberger, +11 authors, Henning Lauterbach.
Nat Commun, 2019 Nov 07; 10(1). PMID: 31695037    Free PMC article.
Nanoparticle Delivery of Immunostimulatory Agents for Cancer Immunotherapy.
Jia Zhuang, Maya Holay, +3 authors, Liangfang Zhang.
Theranostics, 2019 Nov 07; 9(25). PMID: 31695803    Free PMC article.
Review.
Coley's immunotherapy revived: Innate immunity as a link in priming cancer cells for an attack by adaptive immunity.
Ondrej Uher, Veronika Caisova, +5 authors, Karel Pacak.
Semin Oncol, 2019 Nov 20; 46(4-5). PMID: 31739997    Free PMC article.
Review.
Modulation of Immunosuppression by Oligonucleotide-Based Molecules and Small Molecules Targeting Myeloid-Derived Suppressor Cells.
Jihyun Lim, Aram Lee, Hee Gu Lee, Jong-Seok Lim.
Biomol Ther (Seoul), 2019 Aug 23; 28(1). PMID: 31431006    Free PMC article.
Review.
TAM Family Receptor Kinase Inhibition Reverses MDSC-Mediated Suppression and Augments Anti-PD-1 Therapy in Melanoma.
Alisha Holtzhausen, William Harris, +9 authors, H Shelton Earp.
Cancer Immunol Res, 2019 Aug 28; 7(10). PMID: 31451482    Free PMC article.
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.
Optimized antiangiogenic reprogramming of the tumor microenvironment potentiates CD40 immunotherapy.
Abhishek S Kashyap, Martina Schmittnaegel, +18 authors, Alfred Zippelius.
Proc Natl Acad Sci U S A, 2020 Jan 01; 117(1). PMID: 31889004    Free PMC article.
Tumor-Infiltrating Immunosuppressive Cells in Cancer-Cell Plasticity, Tumor Progression and Therapy Response.
Laura Lorenzo-Sanz, Purificación Muñoz.
Cancer Microenviron, 2019 Oct 05; 12(2-3). PMID: 31583529    Free PMC article.
Implications for Tumor Microenvironment and Epithelial Crosstalk in the Management of Gastrointestinal Cancers.
Yang Ge, C Benedikt Westphalen, +2 authors, Nathaniel Weygant.
J Oncol, 2020 Feb 23; 2019. PMID: 32082375    Free PMC article.
Review.
The making and function of CAR cells.
Maja Zabel, Peter A Tauber, Winfried F Pickl.
Immunol Lett, 2019 Jun 11; 212. PMID: 31181279    Free PMC article.
Review.
Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer.
Taylor T Chrisikos, Yifan Zhou, +3 authors, Haiyan S Li.
Mol Immunol, 2018 Mar 20; 110. PMID: 29549977    Free PMC article.
Review.
Radiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer.
Andrew J Rech, Hannah Dada, +4 authors, Robert H Vonderheide.
Cancer Res, 2018 May 31; 78(15). PMID: 29844122    Free PMC article.
An update: emerging drugs to treat squamous cell carcinomas of the head and neck.
Yoon Se Lee, Daniel E Johnson, Jennifer R Grandis.
Expert Opin Emerg Drugs, 2018 Nov 01; 23(4). PMID: 30376740    Free PMC article.
Review.
Stimulating T Cells Against Cancer With Agonist Immunostimulatory Monoclonal Antibodies.
Xue Han, Matthew D Vesely.
Int Rev Cell Mol Biol, 2019 Jan 13; 342. PMID: 30635089    Free PMC article.
Review.
A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity.
Hayley S Ma, Bibhav Poudel, +9 authors, Elizabeth M Jaffee.
Cancer Immunol Res, 2019 Jan 16; 7(3). PMID: 30642833    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.
Nat Commun, 2019 Sep 29; 10(1). PMID: 31562320    Free PMC article.
Novel therapeutic strategies and perspectives for metastatic pancreatic cancer: vaccine therapy is more than just a theory.
Wenhao Luo, Gang Yang, +8 authors, Taiping Zhang.
Cancer Cell Int, 2020 Mar 12; 20. PMID: 32158356    Free PMC article.
Review.
Concepts for agonistic targeting of CD40 in immuno-oncology.
David M Richards, Julian P Sefrin, +2 authors, Christian Merz.
Hum Vaccin Immunother, 2019 Aug 14; 16(2). PMID: 31403344    Free PMC article.
Review.
Tumor endothelial cell up-regulation of IDO1 is an immunosuppressive feed-back mechanism that reduces the response to CD40-stimulating immunotherapy.
Maria Georganaki, Mohanraj Ramachandran, +15 authors, Anna Dimberg.
Oncoimmunology, 2020 Apr 02; 9(1). PMID: 32231867    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.
Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting.
Alexey V Baldin, Lyudmila V Savvateeva, Alexandr V Bazhin, Andrey A Zamyatnin.
Cancers (Basel), 2020 Mar 11; 12(3). PMID: 32150821    Free PMC article.
Review.
Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy.
Katherine M Audsley, Alison M McDonnell, Jason Waithman.
Cells, 2020 Mar 04; 9(3). PMID: 32121071    Free PMC article.
Review.
Inhibition of Hedgehog signaling reprograms the dysfunctional immune microenvironment in breast cancer.
Ann Hanna, Brandon J Metge, +5 authors, Lalita A Shevde.
Oncoimmunology, 2019 Feb 07; 8(3). PMID: 30723576    Free PMC article.
Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity.
Alexander H Morrison, Mark S Diamond, +2 authors, Robert H Vonderheide.
Proc Natl Acad Sci U S A, 2020 Mar 28; 117(14). PMID: 32213589    Free PMC article.
Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy.
Christina Claus, Claudia Ferrara, +54 authors, Pablo Umaña.
Sci Transl Med, 2019 Jun 14; 11(496). PMID: 31189721    Free PMC article.
Highly Cited.
Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs.
Kelsey Roe, Geraldine L Shu, +3 authors, Edward A Clark.
J Immunol, 2019 Sep 06; 203(7). PMID: 31484732    Free PMC article.
Antiangiogenic immunotherapy suppresses desmoplastic and chemoresistant intestinal tumors in mice.
Simone Ragusa, Borja Prat-Luri, +17 authors, Tatiana V Petrova.
J Clin Invest, 2020 Feb 06; 130(3). PMID: 32015230    Free PMC article.
Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity.
Xiaojie Yu, H T Claude Chan, +13 authors, Mark S Cragg.
Cancer Cell, 2020 May 23; 37(6). PMID: 32442402    Free PMC article.
CD40 agonist-induced IL-12p40 potentiates hepatotoxicity.
Caroline Bonnans, Graham Thomas, +10 authors, Yan Qu.
J Immunother Cancer, 2020 Jun 01; 8(1). PMID: 32474414    Free PMC article.
Novel Targets for the Treatment of Melanoma.
Lara Ambrosi, Shaheer Khan, Richard D Carvajal, Jessica Yang.
Curr Oncol Rep, 2019 Nov 07; 21(11). PMID: 31696329
Review.
Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations.
Todd A Aguilera, Eslam A Elghonaimy, +10 authors, Amato J Giaccia.
Clin Cancer Res, 2020 Feb 27; 26(12). PMID: 32098769    Free PMC article.
Line-selective macrophage activation with an anti-CD40 antibody drives a hemophagocytic syndrome in mice.
Giada Ingoglia, Ayla Yalamanoglu, +8 authors, Florence Vallelian.
Blood Adv, 2020 Jun 20; 4(12). PMID: 32559293    Free PMC article.
Brain immunology and immunotherapy in brain tumours.
John H Sampson, Michael D Gunn, Peter E Fecci, David M Ashley.
Nat Rev Cancer, 2019 Dec 07; 20(1). PMID: 31806885    Free PMC article.
Review.
Identification of Potential Key Genes and Pathways for Inflammatory Breast Cancer Based on GEO and TCGA Databases.
Qing Lv, Yansong Liu, +3 authors, Dong Meng.
Onco Targets Ther, 2020 Jul 02; 13. PMID: 32606769    Free PMC article.
CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells.
Rebeca Arroyo Hornero, Christos Georgiadis, +8 authors, Joanna Hester.
Commun Biol, 2020 Jul 16; 3(1). PMID: 32665635    Free PMC article.
Dendritic cell vaccination and CD40-agonist combination therapy licenses T cell-dependent antitumor immunity in a pancreatic carcinoma murine model.
Sai Ping Lau, Nadine van Montfoort, +18 authors, Casper H J van Eijck.
J Immunother Cancer, 2020 Jul 22; 8(2). PMID: 32690771    Free PMC article.
Myeloid Cell-Targeted Nanocarriers Efficiently Inhibit Cellular Inhibitor of Apoptosis for Cancer Immunotherapy.
Peter D Koch, Christopher B Rodell, +2 authors, Ralph Weissleder.
Cell Chem Biol, 2020 Jan 07; 27(1). PMID: 31902676    Free PMC article.
Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.
Lukas Amon, Lukas Hatscher, +2 authors, Christian H K Lehmann.
Pharmaceutics, 2020 Jul 18; 12(7). PMID: 32674488    Free PMC article.
Review.
Combination of thermally ablative focused ultrasound with gemcitabine controls breast cancer via adaptive immunity.
Natasha D Sheybani, Alexandra R Witter, +3 authors, Richard J Price.
J Immunother Cancer, 2020 Aug 21; 8(2). PMID: 32819975    Free PMC article.
Immunotherapy and pancreatic cancer: unique challenges and potential opportunities.
Kate Young, Daniel J Hughes, David Cunningham, Naureen Starling.
Ther Adv Med Oncol, 2018 Dec 24; 10. PMID: 30574212    Free PMC article.
Review.
Enhancing Dendritic Cell Therapy in Solid Tumors with Immunomodulating Conventional Treatment.
Robert A Belderbos, Joachim G J V Aerts, Heleen Vroman.
Mol Ther Oncolytics, 2019 Apr 26; 13. PMID: 31020037    Free PMC article.
Review.
Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy.
Sebastian Chrétien, Ioannis Zerdes, +2 authors, Theodoros Foukakis.
Cancers (Basel), 2019 May 08; 11(5). PMID: 31060337    Free PMC article.
Review.
A replication-incompetent CD154/40L recombinant vaccinia virus induces direct and macrophage-mediated antitumor effects in vitro and in vivo.
Valeria Governa, Alvaro Brittoli, +7 authors, Emanuele Trella.
Oncoimmunology, 2019 May 10; 8(5). PMID: 31069131    Free PMC article.
The Significant Reduction or Complete Eradication of Subcutaneous and Metastatic Lesions in a Pheochromocytoma Mouse Model after Immunotherapy Using Mannan-BAM, TLR Ligands, and Anti-CD40.
Veronika Caisova, Liping Li, +14 authors, Karel Pacak.
Cancers (Basel), 2019 May 15; 11(5). PMID: 31083581    Free PMC article.
Costimulatory and coinhibitory immune checkpoint receptors in head and neck cancer: unleashing immune responses through therapeutic combinations.
Ruth J Davis, Robert L Ferris, Nicole C Schmitt.
Cancers Head Neck, 2016 Oct 01; 1. PMID: 31093342    Free PMC article.
Review.
Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients.
Jean-Pascal Machiels, Carlos Gomez-Roca, +21 authors, Philippe Cassier.
J Immunother Cancer, 2020 Oct 25; 8(2). PMID: 33097612    Free PMC article.
Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations.
Madyson Colton, Eleanor J Cheadle, Jamie Honeychurch, Tim M Illidge.
Radiat Oncol, 2020 Nov 06; 15(1). PMID: 33148287    Free PMC article.
Review.
Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists.
Dana A Emerson, William L Redmond.
BioDrugs, 2018 Apr 11; 32(3). PMID: 29637478    Free PMC article.
Review.
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.
J Immunother Cancer, 2020 Nov 18; 8(2). PMID: 33199513    Free PMC article.
Checkpoint immunotherapy in head and neck cancers.
Paul Zolkind, Ravindra Uppaluri.
Cancer Metastasis Rev, 2017 Aug 25; 36(3). PMID: 28836124    Free PMC article.
Review.
Immunotherapy Targeting Tumor-Associated Macrophages.
Yafei Liu, Rongsi Wang.
Front Med (Lausanne), 2020 Dec 01; 7. PMID: 33251232    Free PMC article.
Review.
Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches.
Tim F Greten, Xin W Wang, Firouzeh Korangy.
Gut, 2015 Feb 11; 64(5). PMID: 25666193    Free PMC article.
Highly Cited. Review.
Emerging immunotherapies for bladder cancer.
Joseph W Kim, Yusuke Tomita, Jane Trepel, Andrea B Apolo.
Curr Opin Oncol, 2015 Mar 27; 27(3). PMID: 25811346    Free PMC article.
Review.
Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update.
Hanley N Abramson.
Int J Mol Sci, 2018 Dec 14; 19(12). PMID: 30544512    Free PMC article.
Review.
Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment.
Chin-King Looi, Felicia Fei-Lei Chung, +3 authors, Chun-Wai Mai.
J Exp Clin Cancer Res, 2019 Apr 17; 38(1). PMID: 30987642    Free PMC article.
Highly Cited. Review.
Advances in engineering local drug delivery systems for cancer immunotherapy.
Peter Abdou, Zejun Wang, +4 authors, Zhen Gu.
Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2020 Apr 08; 12(5). PMID: 32255276    Free PMC article.
Review.
Designed proteins assemble antibodies into modular nanocages.
Robby Divine, Ha V Dang, +27 authors, David Baker.
bioRxiv, 2020 Dec 11;. PMID: 33299994    Free PMC article.
Targeting co-stimulatory molecules in autoimmune disease.
Natalie M Edner, Gianluca Carlesso, James S Rush, Lucy S K Walker.
Nat Rev Drug Discov, 2020 Sep 18; 19(12). PMID: 32939077
Review.
Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system.
Xiaohui Wang, Zhiqiang Wu, +3 authors, Weidong Han.
Front Med, 2020 Aug 15; 14(6). PMID: 32794014
Review.
Immune-Checkpoint Inhibitors in B-Cell Lymphoma.
Marc Armengol, Juliana Carvalho Santos, +3 authors, Gaël Roué.
Cancers (Basel), 2021 Jan 13; 13(2). PMID: 33430146    Free PMC article.
Review.
Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR.
Marta Compte, Seandean L Harwood, +9 authors, Luis Alvarez-Vallina.
Front Immunol, 2021 Jan 26; 11. PMID: 33488625    Free PMC article.
Next-Generation Immunotherapies to Improve Anticancer Immunity.
Yaoyao Shi, Katarzyna Tomczak, +3 authors, Cara Haymaker.
Front Pharmacol, 2021 Jan 29; 11. PMID: 33505304    Free PMC article.
Review.
Immunotherapy in Colorectal Cancer: Current and Future Strategies.
Akira Ooki, Eiji Shinozaki, Kensei Yamaguchi.
J Anus Rectum Colon, 2021 Feb 05; 5(1). PMID: 33537496    Free PMC article.
Review.
A Hepatitis B Virus-Derived Peptide Exerts an Anticancer Effect via TNF/iNOS-producing Dendritic Cells in Tumor-Bearing Mouse Model.
Soo-Bin Yang, Mi-Hyun Lee, +2 authors, Bum-Joon Kim.
Cancers (Basel), 2021 Jan 28; 13(3). PMID: 33499256    Free PMC article.
Induction of Immune Response Against Metastatic Tumors via Vaccination of Mannan-BAM, TLR Ligands and Anti-CD40 Antibody (MBTA).
Rogelio Medina, Herui Wang, +15 authors, Zhengping Zhuang.
Adv Ther (Weinh), 2021 Mar 13; 3(9). PMID: 33709018    Free PMC article.
Combination therapies utilizing neoepitope-targeted vaccines.
Karin L Lee, Jeffrey Schlom, Duane H Hamilton.
Cancer Immunol Immunother, 2020 Oct 10; 70(4). PMID: 33033852    Free PMC article.
Review.
Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies.
Vassilis Genoud, Denis Migliorini.
Int J Mol Sci, 2021 Apr 04; 22(7). PMID: 33800593    Free PMC article.
Review.
Mannan-BAM, TLR Ligands, Anti-CD40 Antibody (MBTA) Vaccine Immunotherapy: A Review of Current Evidence and Applications in Glioblastoma.
Pashayar P Lookian, David Zhao, +5 authors, Zhengping Zhuang.
Int J Mol Sci, 2021 Apr 04; 22(7). PMID: 33810617    Free PMC article.
Review.
IL-1α Mediates Innate and Acquired Resistance to Immunotherapy in Melanoma.
Shubhra Singh, Zhilan Xiao, +10 authors, Manisha Singh.
J Immunol, 2021 Mar 17; 206(8). PMID: 33722878    Free PMC article.
Cancer Vaccines, Adjuvants, and Delivery Systems.
Samantha J Paston, Victoria A Brentville, Peter Symonds, Lindy G Durrant.
Front Immunol, 2021 Apr 17; 12. PMID: 33859638    Free PMC article.
Review.
The Latest Advancement in Pancreatic Ductal Adenocarcinoma Therapy: A Review Article for the Latest Guidelines and Novel Therapies.
Marwa Elsayed, Maen Abdelrahim.
Biomedicines, 2021 May 01; 9(4). PMID: 33917380    Free PMC article.
Review.
Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy.
Tiziana Cotechini, Aline Atallah, Arielle Grossman.
Cells, 2021 May 01; 10(4). PMID: 33924237    Free PMC article.
Review.
Nanoparticle-based approaches to target the lymphatic system for antitumor treatment.
Xingzhou Peng, Junjie Wang, +2 authors, Zhihong Zhang.
Cell Mol Life Sci, 2021 May 09; 78(12). PMID: 33963442
Review.
Immunotherapies targeting stimulatory pathways and beyond.
Julian A Marin-Acevedo, ErinMarie O Kimbrough, +2 authors, Yanyan Lou.
J Hematol Oncol, 2021 May 14; 14(1). PMID: 33980266    Free PMC article.
Review.
Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy.
Benjamin Wolfson, S Elizabeth Franks, James W Hodge.
Vaccines (Basel), 2021 Jun 03; 9(5). PMID: 34063388    Free PMC article.
Review.
Sequential Treatment of Bioresponsive Nanoparticles Elicits Antiangiogenesis and Apoptosis and Synergizes with a CD40 Agonist for Antitumor Immunity.
Xiang Ling, Xiaomin Jiang, +4 authors, Wenbin Lin.
ACS Nano, 2020 Dec 22; 15(1). PMID: 33347262    Free PMC article.
VISTA is an activating receptor in human monocytes.
Bryan M Rogers, Laura Smith, +14 authors, Gabriel R Starbeck-Miller.
J Exp Med, 2021 Jun 10; 218(8). PMID: 34106206    Free PMC article.
C4b-binding protein α-chain enhances antitumor immunity by facilitating the accumulation of tumor-infiltrating lymphocytes in the tumor microenvironment in pancreatic cancer.
Kosuke Sasaki, Shigetsugu Takano, +6 authors, Masayuki Ohtsuka.
J Exp Clin Cancer Res, 2021 Jun 26; 40(1). PMID: 34167573    Free PMC article.
Co-Stimulatory versus Cell Death Aspects of Agonistic CD40 Monoclonal Antibody Selicrelumab in Chronic Lymphocytic Leukemia.
Raquel Delgado, Karoline Kielbassa, +5 authors, Eric Eldering.
Cancers (Basel), 2021 Jul 03; 13(12). PMID: 34205588    Free PMC article.
CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies.
Timothy N J Bullock.
Cell Mol Immunol, 2021 Jul 21; 19(1). PMID: 34282297    Free PMC article.
Review.
Cellular based immunotherapy for primary liver cancer.
Yuanyuan Zheng, Yan Li, +8 authors, Chuanyong Guo.
J Exp Clin Cancer Res, 2021 Aug 11; 40(1). PMID: 34372912    Free PMC article.
Review.
Identification of Immune Cell Infiltration in Murine Pheochromocytoma during Combined Mannan-BAM, TLR Ligand, and Anti-CD40 Antibody-Based Immunotherapy.
Ondrej Uher, Thanh-Truc Huynh, +10 authors, Karel Pacak.
Cancers (Basel), 2021 Aug 28; 13(16). PMID: 34439097    Free PMC article.
Macrophages Impair TLR9 Agonist Antitumor Activity through Interacting with the Anti-PD-1 Antibody Fc Domain.
Simone Camelliti, Valentino Le Noci, +12 authors, Michele Sommariva.
Cancers (Basel), 2021 Aug 28; 13(16). PMID: 34439233    Free PMC article.
CD40 Agonist Monoclonal Antibody-Mediated Hepatitis in TNF-Receptor 1 Gene Knockout Mice.
Oksana Raabe, Thomas Birchler, Hubert Rehrauer, Elisabeth Eppler.
Biomedicines, 2021 Aug 28; 9(8). PMID: 34440067    Free PMC article.
A CLDN18.2-Targeting Bispecific T Cell Co-Stimulatory Activator for Cancer Immunotherapy.
Jie Liang, Huihui Zhang, +7 authors, Xuanming Yang.
Cancer Manag Res, 2021 Sep 16; 13. PMID: 34522140    Free PMC article.
Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin).
Vassilis Genoud, Felipe I Espinoza, +6 authors, Paul R Walker.
JCI Insight, 2021 Aug 18; 6(18). PMID: 34403371    Free PMC article.
Immunotoxins Immunotherapy against Hepatocellular Carcinoma: A Promising Prospect.
Mohammad Heiat, Hamid Hashemi Yeganeh, Seyed Moayed Alavian, Ehsan Rezaie.
Toxins (Basel), 2021 Oct 23; 13(10). PMID: 34679012    Free PMC article.
Review.
Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1.
Hsuan-Chen Liu, Dixita I Viswanath, +16 authors, Alessandro Grattoni.
Int J Radiat Oncol Biol Phys, 2020 Aug 10; 110(2). PMID: 32768562    Free PMC article.
Designed proteins assemble antibodies into modular nanocages.
Robby Divine, Ha V Dang, +27 authors, David Baker.
Science, 2021 Apr 03; 372(6537). PMID: 33795432    Free PMC article.
Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives.
Marije J Voskamp, Shuang Li, +3 authors, Niels Bovenschen.
Cancers (Basel), 2021 Nov 14; 13(21). PMID: 34771550    Free PMC article.
Review.
Double Strike Approach for Tumor Attack: Engineering T Cells Using a CD40L:CD28 Chimeric Co-Stimulatory Switch Protein for Enhanced Tumor Targeting in Adoptive Cell Therapy.
Luis Felipe Olguín-Contreras, Anna N Mendler, +2 authors, Elfriede Noessner.
Front Immunol, 2021 Dec 17; 12. PMID: 34912334    Free PMC article.
Immune System in Action.
Bettzy Stephen, Joud Hajjar.
Adv Exp Med Biol, 2022 Jan 02; 1342. PMID: 34972961
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.
Front Immunol, 2022 Feb 01; 12. PMID: 35095862    Free PMC article.
LncRNA PCGEM1 in Human Cancers: Functions, Mechanisms and Promising Clinical Utility.
Yuanshuai Su, Xinyu Gu, +3 authors, Lanjuan Li.
Front Oncol, 2022 Mar 11; 12. PMID: 35265529    Free PMC article.
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.
J Immunother Cancer, 2022 Mar 17; 10(3). PMID: 35292514    Free PMC article.