CD40 agonist antibodies in cancer immunotherapy

T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions

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A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell

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Help for cytotoxic-T-cell responses is mediated by CD40 signalling

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CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans

Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., et al. (2011) · Science · doi:10.1126/science.1198443 · Cited by 1,678 · see citing works

Molecular mechanism and function of CD40/CD40L engagement in the immune system

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CD40 AND CD154 IN CELL-MEDIATED IMMUNITY

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CD40-CD40 ligand

van Kooten, C., & Banchereau, J. (2000) · Journal of Leukocyte Biology · doi:10.1002/jlb.67.1.2 · Cited by 1,413 · see citing works

CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade

Giavridis, T., van der Stegen, S. J. C., Eyquem, J., Hamieh, M., Piersigilli, A., & Sadelain, M. (2018) · Nature Medicine · doi:10.1038/s41591-018-0041-7 · Cited by 1,272 · see citing works

Dynamics of the immune reaction to pancreatic cancer from inception to invasion

Clark, C. E., Hingorani, S. R., Mick, R., Combs, C., Tuveson, D. A., & Vonderheide, R. H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0175 · Cited by 990 · see citing works

Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer

Bayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.025 · Cited by 947 · see citing works

Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy

Li, J., Byrne, K. T., Yan, F., Yamazoe, T., Chen, Z., Baslan, T., Richman, L. P., Lin, J., Sun, Y. H., Rech, A. J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.06.006 · Cited by 738 · see citing works

Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia

Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G., & Bar-Sagi, D. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.024 · Cited by 721 · see citing works

Clinical Activity and Immune Modulation in Cancer Patients Treated With CP-870,893, a Novel CD40 Agonist Monoclonal Antibody

Vonderheide, R. H., Flaherty, K. T., Khalil, M., Stumacher, M., Bajor, D. L., Hutnick, N. A., Sullivan, P., Mahany, J. J., Gallagher, M., Kramer, A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.3311 · Cited by 513 · see citing works

Immunotherapy and Prevention of Pancreatic Cancer

Morrison, A. H., Byrne, K. T., & Vonderheide, R. H. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.04.001 · Cited by 469 · see citing works

CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor vaccine efficacy

Diehl, L., den Boer, A. T., Schoenberger, S. P., van der Voort, E. I. H., Schumacher, T. N., Melief, C. J. M., Offringa, R., & Toes, R. E. M. (1999) · Nature Medicine · doi:10.1038/10495 · Cited by 468 · see citing works

Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma

Winograd, R., Byrne, K. T., Evans, R. A., Odorizzi, P. M., Meyer, A. R. L., Bajor, D. L., Clendenin, C., Stanger, B. Z., Furth, E. E., Wherry, E. J., et al. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0215 · Cited by 459 · see citing works

A Phase I Study of an Agonist CD40 Monoclonal Antibody (CP-870,893) in Combination with Gemcitabine in Patients with Advanced Pancreatic Ductal Adenocarcinoma

Beatty, G. L., Torigian, D. A., Chiorean, E. G., Saboury, B., Brothers, A., Alavi, A. A., Troxel, A. B., Sun, W., Teitelbaum, U. R., Vonderheide, R. H., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1320 · Cited by 458 · see citing works

Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities

Balachandran, V. P., Beatty, G. L., & Dougan, S. K. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.038 · Cited by 444 · see citing works

Agonistic CD40 Antibodies and Cancer Therapy

Vonderheide, R. H., & Glennie, M. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2064 · Cited by 443 · see citing works

CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help

French, R. R., Chan, H. T. C., Tutt, A. L., & Glennie, M. J. (1999) · Nature Medicine · doi:10.1038/8426 · Cited by 426 · see citing works

Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40

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CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy.

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Inhibitory Fcγ Receptor Engagement Drives Adjuvant and Anti-Tumor Activities of Agonistic CD40 Antibodies

Li, F., & Ravetch, J. V. (2011) · Science · doi:10.1126/science.1206954 · Cited by 331 · see citing works

The Immune Revolution: A Case for Priming, Not Checkpoint

Vonderheide, R. H. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.008 · Cited by 294 · see citing works

Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6Clow F4/80+ Extratumoral Macrophages

Beatty, G. L., Winograd, R., Evans, R. A., Long, K. B., Luque, S. L., Lee, J. W., Clendenin, C. J., Gladney, W. L., Knoblock, D. M., Guirnalda, P. D., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.010 · Cited by 293 · see citing works

CD40 stimulation obviates innate sensors and drives T cell immunity in cancer

Byrne, K. T., & Vonderheide, R. H. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.058 · Cited by 282 · see citing works

IFNγ and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma

Long, K. B., Gladney, W. L., Tooker, G. M., Graham, K. L., Fraietta, J. A., & Beatty, G. L. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1032 · Cited by 272 · see citing works

Eradication of established tumors in mice by a combination antibody-based therapy

Uno, T., Takeda, K., Kojima, Y., Yoshizawa, H., Akiba, H., Mittler, R. S., Gejyo, F., Okumura, K., Yagita∥, H., & Smyth, M. J. (2006) · Nature Medicine · doi:10.1038/nm1405 · Cited by 257 · see citing works

CXCR2-Dependent Accumulation of Tumor-Associated Neutrophils Regulates T-cell Immunity in Pancreatic Ductal Adenocarcinoma

Chao, T., Furth, E. E., & Vonderheide, R. H. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0188 · Cited by 248 · see citing works

Interaction with FcγRIIB Is Critical for the Agonistic Activity of Anti-CD40 Monoclonal Antibody

White, A. L., Chan, H. T. C., Roghanian, A., French, R. R., Mockridge, C. I., Tutt, A. L., Dixon, S. V., Ajona, D., Verbeek, J. S., Al‐Shamkhani, A., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101135 · Cited by 227 · see citing works

Phase I Study of Recombinant Human CD40 Ligand in Cancer Patients

Vonderheide, R. H., Dutcher, J. P., Anderson, J. E., Eckhardt, S. G., Stephans, K. F., Razvillas, B., Garl, S., Butine, M. D., Perry, V. P., Armitage, R. J., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.13.3280 · Cited by 223 · see citing works

CD40 stimulation leads to effective therapy of CD40 − tumors through induction of strong systemic cytotoxic T lymphocyte immunity

van Mierlo, G. J. D., den Boer, A. T., Medema, J. P., van der Voort, E. I. H., Fransen, M. F., Offringa, R., Melief, C. J. M., & Toes, R. E. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082107699 · Cited by 222 · see citing works

Essential Cytoplasmic Translocation of a Cytokine Receptor–Assembled Signaling Complex

Matsuzawa, A., Tseng, P., Vallabhapurapu, S., Luo, J., Zhang, W., Wang, H., Vignali, D. A. A., Gallagher, E. D., & Karin, M. (2008) · Science · doi:10.1126/science.1157340 · Cited by 217 · see citing works

Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors

Vonderheide, R. H., Burg, J. M., Mick, R., Trosko, J. A., Li, D., Shaik, M. N., Tolcher, A. W., & Hamid, O. (2013) · OncoImmunology · doi:10.4161/onci.23033 · Cited by 202 · see citing works

Prospect of Targeting the CD40 Pathway for Cancer Therapy

Vonderheide, R. H. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1893 · Cited by 186 · see citing works

Conformation of the Human Immunoglobulin G2 Hinge Imparts Superagonistic Properties to Immunostimulatory Anticancer Antibodies

White, A. L., Chan, H. T. C., French, R. R., Willoughby, J. E., Mockridge, C. I., Roghanian, A., Penfold, C. A., Booth, S. G., Dodhy, A., Polak, M. E., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.11.001 · Cited by 173 · see citing works

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

Dahan, R., Barnhart, B. C., Li, F., Yamniuk, A. P., Korman, A. J., & Ravetch, J. V. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.001 · Cited by 164 · see citing works

Local Activation of CD8 T Cells and Systemic Tumor Eradication without Toxicity via Slow Release and Local Delivery of Agonistic CD40 Antibody

Fransen, M. F., Sluijter, M., Morreau, H. M., Arens, R., & Melief, C. J. M. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2888 · Cited by 153 · see citing works

Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors

Rüter, J., Antonia, S. J., Burris, H. A., Huhn, R. D., & Vonderheide, R. H. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.10.13251 · Cited by 148 · see citing works

First‐in‐human study with intratumoral administration of a CD40 agonistic antibody, ADC‐1013, in advanced solid malignancies

Irenaeus, S., Nielsen, D. L., Ellmark, P., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32141 · Cited by 147 · see citing works

Induced PD-L1 Expression Mediates Acquired Resistance to Agonistic Anti-CD40 Treatment

Zippelius, A., Schreiner, J., Herzig, P., & Müller, P. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0226 · Cited by 144 · see citing works

Metastatic progression is associated with dynamic changes in the local microenvironment

Aiello, N. M., Bajor, D. L., Norgard, R. J., Sahmoud, A., Bhagwat, N., Pham, M. N., Cornish, T. C., Iacobuzio–Donahue, C. A., Vonderheide, R. H., & Stanger, B. Z. (2016) · Nature Communications · doi:10.1038/ncomms12819 · Cited by 135 · see citing works

CD40 Ligation Activates Murine Macrophages via an IFN-γ-Dependent Mechanism Resulting in Tumor Cell Destruction In Vitro

Buhtoiarov, I. N., Lum, H. D., Berke, G., Paulnock, D. M., Sondel, P. M., & Rakhmilevich, A. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.6013 · Cited by 125 · see citing works

A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell–Mediated Anticancer Activity

Ma, H. S., Poudel, B., Torres, E. T. R., Sidhom, J.-W., Robinson, T. M., Christmas, B. J., Scott, B., Cruz, K. A., Woolman, S., Wall, V., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0061 · Cited by 124 · see citing works

Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity

Knorr, D. A., Dahan, R., & Ravetch, J. V. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810566115 · Cited by 120 · see citing works

Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma

Bajor, D. L., Mick, R., Riese, M. J., Huang, A. C., Sullivan, B. J., Richman, L. P., Torigian, D. A., George, S. M., Stelekati, E., Chen, F., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1468956 · Cited by 119 · see citing works

Radiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer

Rech, A. J., Dada, H., Kotzin, J. J., Henao‐Mejia, J., Minn, A. J., Victor, C. T.-S., & Vonderheide, R. H. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3821 · Cited by 115 · see citing works

Clinical and Biological Effects of an Agonist Anti-CD40 Antibody: A Cancer Research UK Phase I Study

Johnson, P., Challis, R., Chowdhury, F., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2355 · Cited by 110 · see citing works

The Human Agonistic CD40 Antibody ADC-1013 Eradicates Bladder Tumors and Generates T-cell–Dependent Tumor Immunity

Mangsbo, S. M., Broos, S., Fletcher, E. A. K., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0913 · Cited by 106 · see citing works

A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma

Nowak, A. K., Cook, A., McDonnell, A. M., Millward, M., Creaney, J., Francis, R. J., Hasani, A., Segal, A., Musk, A. W., Turlach, B. A., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv387 · Cited by 100 · see citing works

Locally Delivered CD40 Agonist Antibody Accumulates in Secondary Lymphoid Organs and Eradicates Experimental Disseminated Bladder Cancer

Sandin, L. C., Orlova, A., Gustafsson, E., Ellmark, P., Максимилианович, Т. В., Tötterman, T. H., & Mangsbo, S. M. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0067 · Cited by 96 · see citing works

Agonistic CD40 mAb-Driven IL12 Reverses Resistance to Anti-PD1 in a T-cell–Rich Tumor

Ngiow, S. F., Young, A., Blake, S. J., Hill, G. R., Yagita∥, H., Teng, M. W. L., Korman, A. J., & Smyth, M. J. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-2141 · Cited by 92 · see citing works

Role of Crosslinking for Agonistic CD40 Monoclonal Antibodies as Immune Therapy of Cancer

Richman, L. P., & Vonderheide, R. H. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0152 · Cited by 91 · see citing works

The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice

Gladue, R. P., Paradis, T. J., Cole, S. H., Donovan, C. B., Nelson, R. T., Alpert, R., Gardner, J., Natoli, E. J., Elliott, E. A., Shepard, R. M., et al. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1014-6 · Cited by 68 · see citing works

The Use of Agonistic Anti-CD40 Therapy in Treatments for Cancer

Khong, A., Nelson, D. J., Nowak, A. K., Lake, R., & Robinson, B. W. S. (2012) · International Reviews of Immunology · doi:10.3109/08830185.2012.698338 · Cited by 67 · see citing works

CSF-1R–Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody Is Given before but Not after Chemotherapy

Byrne, K. T., Leisenring, N. H., Bajor, D. L., & Vonderheide, R. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600146 · Cited by 62 · see citing works

Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy

Vitale, L. A., Thomas, L. J., He, L.-Z., et al. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2267-0 · Cited by 59 · see citing works

Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage

Medina‐Echeverz, J., Ma, C., Duffy, A. G., Eggert, T., Hawk, N. V., Kleiner, D. E., Korangy, F., & Greten, T. F. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0182 · Cited by 54 · see citing works

Immune Activation and a 9-Year Ongoing Complete Remission Following CD40 Antibody Therapy and Metastasectomy in a Patient with Metastatic Melanoma

Bajor, D. L., Xu, X., Torigian, D. A., Mick, R., Garcia, L. R., Richman, L. P., Desmarais, C., Nathanson, K. L., Schuchter, L. M., Kalos, M. D., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0154 · Cited by 43 · see citing works

CD40 ligation in vivo can induce T cell independent antitumor effects even against immunogenic tumors

Rakhmilevich, A. L., Buhtoiarov, I. N., Malkovský, M., & Sondel, P. M. (2008) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-007-0447-4 · Cited by 37 · see citing works

SEA-CD40, a non-fucosylated CD40 agonist: Interim results from a phase 1 study in advanced solid tumors.

Grilley‐Olson, J. E., Curti, B. D., Smith, D. C., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.3093 · Cited by 28 · see citing works

Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters

McDonnell, A. M., Cook, A., Robinson, B. W. S., et al. (2017) · BMC Cancer · doi:10.1186/s12885-017-3403-5 · Cited by 10 · see citing works

Pancreatic cancer: Advances and challenges

Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321 · see citing works

Challenges and Opportunities for Pancreatic Cancer Immunotherapy

Bear, A. S., Vonderheide, R. H., & O'Hara, M. H. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.004 · Cited by 674 · see citing works

The Role of Macrophages in Cancer Development and Therapy

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CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study

O'Hara, M. H., O'Reilly, E. M., Varadhachary, G., Wolff, R. A., Wainberg, Z. A., Ko, A. H., Fisher, G., Rahma, O., Lyman, J. P., Cabanski, C. R., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30532-5 · Cited by 307 · see citing works

The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer

Freed-Pastor, W. A., Lambert, L. J., Ely, Z. A., Pattada, N. B., Bhutkar, A., Eng, G., Mercer, K. L., Garcia, A. P., Lin, L., Rideout, W. M., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.07.007 · Cited by 273 · see citing works

Neoadjuvant Selicrelumab, an agonist CD40 antibody, induces changes in the tumor microenvironment in patients with resectable pancreatic cancer

Byrne, K. T., Betts, C. B., Mick, R., Sivagnanam, S., Bajor, D. L., Laheru, D. A., Chiorean, E. G., O'Hara, M. H., Liudahl, S. M., Newcomb, C., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1047 · Cited by 199 · see citing works

Epithelial and stromal co-evolution and complicity in pancreatic cancer

Hingorani, S. R. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00530-w · Cited by 108 · see citing works

Small molecules targeting protein–protein interactions for cancer therapy

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Antiangiogenic immunotherapy suppresses desmoplastic and chemoresistant intestinal tumors in mice

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Immunotherapies targeting stimulatory pathways and beyond

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Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma

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Species- and agonist-dependent differences in the deactivation-kinetics of P2X 7 receptors

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Being mindful of seven‐transmembrane receptor ‘guests’ when assessing agonist selectivity

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Selective agonists of somatostatin receptor subtype 1 or 2 injected peripherally induce antihyperalgesic effect in two models of visceral hypersensitivity in mice

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Up/Down: A New Method for Determining Agonist Properties

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An analysis of the functional interactions of selected contractile agonists in the guinea pig isolated trachea.

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