Cancers (Basel). 2021 Mar 15;13(6). doi: 10.3390/cancers13061302.
Agonistic CD40 Antibodies in Cancer Treatment.
Cancers
Dijana Djureinovic, Meina Wang, Harriet M Kluger
Affiliations
Affiliations
- Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.
PMID: 33804039
PMCID: PMC8000216 DOI: 10.3390/cancers13061302
Abstract
CD40 is expressed on a variety of antigen-presenting cells. Stimulation of CD40 results in inflammation by upregulation of other costimulatory molecules, increased antigen presentation, maturation (licensing) of dendritic cells, and activation of CD8+ T cells. Here we analyzed gene expression data from The Cancer Genome Atlas in melanoma, renal cell carcinoma, and pancreatic adenocarcinoma and found correlations between CD40 and several genes involved in antigen presentation and T cell function, supporting further exploration of CD40 agonists to treat cancer. Agonist CD40 antibodies have induced anti-tumor effects in several tumor models and the effect has been more pronounced when used in combination with other treatments (immune checkpoint inhibition, chemotherapy, and colony-stimulating factor 1 receptor inhibition). The reduction in tumor growth and ability to reprogram the tumor microenvironment in preclinical models lays the foundation for clinical development of agonistic CD40 antibodies (APX005M, ChiLob7/4, ADC-1013, SEA-CD40, selicrelumab, and CDX-1140) that are currently being evaluated in early phase clinical trials. In this article, we focus on CD40 expression and immunity in cancer, agonistic human CD40 antibodies, and their pre-clinical and clinical development. With the broad pro-inflammatory effects of CD40 and its ligand on dendritic cells and macrophages, and downstream B and T cell activation, agonists of this pathway may enhance the anti-tumor activity of other systemic therapies.
Keywords: CD40; agonistic antibodies; cancer; innate immunity
References
- Cell. 2017 Feb 9;168(4):707-723 - PubMed
- Oncoimmunology. 2018 Aug 20;7(10):e1468956 - PubMed
- Am J Transplant. 2003 Nov;3(11):1341-9 - PubMed
- Blood. 2009 Sep 24;114(13):2649-56 - PubMed
- Cancer Immunol Res. 2015 Apr;3(4):399-411 - PubMed
- Lancet Oncol. 2021 Jan;22(1):118-131 - PubMed
- Lancet Oncol. 2017 Jan;18(1):31-41 - PubMed
- Science. 2011 Mar 25;331(6024):1612-6 - PubMed
- Clin Cancer Res. 2017 Aug 1;23(15):4270-4279 - PubMed
- Immunol Cell Biol. 2011 Feb;89(2):255-67 - PubMed
- Cancer Res. 2016 Nov 1;76(21):6266-6277 - PubMed
- Int J Cancer. 2019 Sep 1;145(5):1189-1199 - PubMed
- Nat Med. 2002 Mar;8(3):247-52 - PubMed
- Adv Drug Deliv Rev. 2016 Apr 1;99(Pt B):180-185 - PubMed
- Int J Biol Macromol. 2019 Mar 1;124:846-853 - PubMed
- Cancer Res. 2006 Jun 15;66(12):6395-404 - PubMed
- Oncoimmunology. 2013 Jan 1;2(1):e23033 - PubMed
- Clin Cancer Res. 2011 Apr 15;17(8):2270-80 - PubMed
- Haematologica. 2010 May;95(5):845-8 - PubMed
- Cancer Biol Ther. 2010 Nov 15;10(10):983-93 - PubMed
- Cytokine. 2001 Nov 21;16(4):131-42 - PubMed
- Hum Immunol. 1993 Jan;36(1):34-40 - PubMed
- Cell Rep. 2016 Jun 21;15(12):2719-32 - PubMed
- J Hepatol. 2020 Dec 1;: - PubMed
- Eur J Immunol. 2005 Nov;35(11):3307-19 - PubMed
- Sci Transl Med. 2012 Mar 28;4(127):127ra37 - PubMed
- Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):541-551 - PubMed
- Cancer Res. 2018 Oct 15;78(20):5891-5900 - PubMed
- Int Rev Immunol. 2012 Aug;31(4):267-78 - PubMed
- Science. 2002 Sep 20;297(5589):2060-3 - PubMed
- Cancer Res. 2003 Aug 1;63(15):4490-6 - PubMed
- Lancet Oncol. 2019 Feb;20(2):297-310 - PubMed
- Clin Cancer Res. 2015 Mar 15;21(6):1321-8 - PubMed
- J Immunol. 2001 Jan 1;166(1):89-94 - PubMed
- J Exp Med. 2018 Mar 5;215(3):877-893 - PubMed
- Nat Rev Clin Oncol. 2019 Mar;16(3):151-167 - PubMed
- J Exp Med. 1998 Dec 7;188(11):2175-80 - PubMed
- Annu Rev Immunol. 1994;12:881-922 - PubMed
- Cancer Immunol Res. 2014 Jan;2(1):19-26 - PubMed
- Int J Cancer. 2014 Oct 15;135(8):1983-8 - PubMed
- Nat Rev Immunol. 2017 Feb;17(2):97-111 - PubMed
- Nat Med. 2004 May;10(5):540-4 - PubMed
- Clin Cancer Res. 2015 Mar 1;21(5):1115-26 - PubMed
- Cancer Cell. 2015 Jan 12;27(1):138-48 - PubMed
- Clin Cancer Res. 2013 Nov 15;19(22):6286-95 - PubMed
- J Immunol. 2016 Jul 1;197(1):179-87 - PubMed
- Lancet Oncol. 2016 Nov;17(11):1558-1568 - PubMed
- J Immunol. 2008 May 15;180(10):6527-35 - PubMed
- Nat Immunol. 2011 Jul 19;12(8):695-708 - PubMed
- J Immunol. 1999 Jul 15;163(2):787-93 - PubMed
- J Immunol. 2011 Aug 15;187(4):1754-63 - PubMed
- N Engl J Med. 2018 Apr 05;378(14):1277-1290 - PubMed
- Cancer Immunol Immunother. 2019 Feb;68(2):233-245 - PubMed
- J Immunother Cancer. 2020 Oct;8(2): - PubMed
- Int J Cancer. 2003 Feb 10;103(4):466-74 - PubMed
- Immunobiology. 2020 Mar;225(2):151899 - PubMed
- Cancer Cell. 2018 Apr 9;33(4):664-675.e4 - PubMed
- J Clin Oncol. 2007 Mar 1;25(7):876-83 - PubMed
- J Exp Med. 1996 Jan 1;183(1):159-67 - PubMed
- Cancer Cell. 2016 Jun 13;29(6):820-831 - PubMed
- J Mol Biol. 2016 Jul 17;428(14):2860-79 - PubMed
- Immunol Rev. 1996 Oct;153:85-106 - PubMed
- Mol Cell Biol. 2000 Aug;20(15):5503-15 - PubMed
- Cancer Cell. 2018 Apr 9;33(4):563-569 - PubMed
- Circ Res. 2011 Nov 11;109(11):1269-79 - PubMed
- J Exp Med. 1987 Oct 1;166(4):1084-97 - PubMed
- Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10691-6 - PubMed
- Science. 2011 Aug 19;333(6045):1030-4 - PubMed
- Blood. 1998 Dec 1;92(11):4150-66 - PubMed
- Cancer Cell. 2016 Sep 12;30(3):500 - PubMed
- Cancer Immunol Res. 2015 Mar;3(3):236-44 - PubMed
- Immunology. 1994 Nov;83(3):430-7 - PubMed
- N Engl J Med. 2017 Oct 5;377(14):1345-1356 - PubMed
- Nat Med. 1999 Jul;5(7):780-7 - PubMed
- N Engl J Med. 2015 Jul 2;373(1):23-34 - PubMed
- J Exp Med. 2018 Mar 5;215(3):859-876 - PubMed
- EBioMedicine. 2021 Feb;64:103160 - PubMed
- N Engl J Med. 2019 Nov 21;381(21):2020-2031 - PubMed
- Cancer Immunol Res. 2014 Nov;2(11):1051-8 - PubMed
- Clin Cancer Res. 2011 Jul 15;17(14):4672-81 - PubMed
- Immunol Rev. 2009 May;229(1):152-72 - PubMed
- Oncotarget. 2016 Apr 5;7(14):18508-20 - PubMed
- Cancer Res. 2018 Aug 1;78(15):4282-4291 - PubMed
- Annu Rev Immunol. 1998;16:111-35 - PubMed
- Front Immunol. 2013 Nov 15;4:376 - PubMed
- J Immunol. 1998 Feb 1;160(3):1224-32 - PubMed
- Oncol Lett. 2011 Jul;2(4):583-589 - PubMed
- Nat Commun. 2017 Nov 10;8(1):1404 - PubMed
- J Immunol. 2008 Sep 1;181(5):3422-31 - PubMed
- J Exp Med. 2004 Mar 15;199(6):775-84 - PubMed
- J Clin Oncol. 2017 Dec 1;35(34):3851-3858 - PubMed
- Annu Rev Immunol. 2002;20:55-72 - PubMed
- J Allergy Clin Immunol. 2002 Sep;110(3):421-8 - PubMed
- Nat Med. 1996 Oct;2(10):1096-103 - PubMed
- Front Cardiovasc Med. 2017 Jun 20;4:40 - PubMed
- Immunology. 2001 Jan;102(1):39-43 - PubMed
- Immunology. 2002 Aug;106(4):456-63 - PubMed
- Oral Oncol. 2014 May;50(5):457-67 - PubMed
- J Exp Med. 2001 Sep 17;194(6):769-79 - PubMed
- Curr Opin Hematol. 2003 Jul;10(4):272-8 - PubMed
- J Exp Med. 2002 Dec 16;196(12):1627-38 - PubMed
- Nat Immunol. 2013 Oct;14(10):1014-22 - PubMed
- Eur J Immunol. 2013 Oct;43(10):2718-29 - PubMed
- Cancer Immunol Res. 2017 Mar;5(3):182-190 - PubMed
- Trends Genet. 1995 Feb;11(2):69-74 - PubMed
- Nature. 1998 Jun 4;393(6684):480-3 - PubMed
- J Immunol. 2004 May 15;172(10):6047-56 - PubMed
- J Immunol. 2011 Apr 1;186(7):4183-90 - PubMed
- Nat Med. 2020 Feb;26(2):193-199 - PubMed
- Oncology (Williston Park). 2010 Dec;24(14):1280-8 - PubMed
- Cancer Immunol Res. 2014 Jan;2(1):80-90 - PubMed
- Ann Oncol. 2015 Dec;26(12):2483-90 - PubMed
Publication Types
Grant support