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Oncotarget. 2020 Sep 22;11(38):3531-3557. doi: 10.18632/oncotarget.27730. eCollection 2020 Sep 22.

Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.

Oncotarget

Fleury Augustin Nsole Biteghe, Neelakshi Mungra, Nyangone Ekome Toung Chalomie, Jean De La Croix Ndong, Jean Engohang-Ndong, Guillaume Vignaux, Eden Padayachee, Krupa Naran, Stefan Barth

Affiliations

  1. Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, CA, USA.
  2. These authors contributed equally to this work.
  3. Medical Biotechnology & Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
  4. Sun Yat-Sen University, Zhongshan Medical School, Guangzhou, China.
  5. Department of Orthopedic Surgery, New York University School of Medicine, New York, NY, USA.
  6. Department of Biological Sciences, Kent State University at Tuscarawas, New Philadelphia, OH, USA.
  7. Arctic Slope Regional Corporation Federal, Beltsville, MD, USA.
  8. Department of Physiology, University of Kentucky, Lexington, KY, USA.
  9. South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

PMID: 33014289 PMCID: PMC7517958 DOI: 10.18632/oncotarget.27730

Abstract

The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.

Keywords: epidermal growth factor receptor (EGFR); recombinant antibody photoimmunoconjugates (rAPCs); recombinant antibody-drug conjugates (rADCs); recombinant immunotoxins (ITs); targeted human cytolytic fusion proteins (hCFPs)

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest. Prof Barth is inventor on several patent applications describing EGFR specific PDT and hCFP. Most of these patents have been assigne

References

  1. Semin Oncol. 1999 Oct;26(5 Suppl 14):74-8 - PubMed
  2. Curr Opin Investig Drugs. 2002 Jul;3(7):1089-91 - PubMed
  3. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10029-33 - PubMed
  4. Theranostics. 2013 Apr 23;3(6):357-65 - PubMed
  5. Chem Commun (Camb). 2014 Nov 18;50(89):13735-8 - PubMed
  6. Ann Oncol. 2015 Oct;26(10):2073-8 - PubMed
  7. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5 - PubMed
  8. Cancer Res. 2003 Apr 15;63(8):1834-7 - PubMed
  9. J Pharm Sci. 2016 Feb;105(2):417-430 - PubMed
  10. Pharmacotherapy. 2016 Jan;36(1):99-116 - PubMed
  11. Immunotherapy. 2014;6(12):1265-78 - PubMed
  12. Cancer Immunol Immunother. 2015 Dec;64(12):1575-86 - PubMed
  13. Cancer Lett. 2016 Oct 28;381(2):323-30 - PubMed
  14. Int J Mol Med. 2005 Feb;15(2):305-13 - PubMed
  15. Nat Med. 2000 Apr;6(4):443-6 - PubMed
  16. Sci Transl Med. 2013 Oct 23;5(208):208ra147 - PubMed
  17. MAbs. 2010 May-Jun;2(3):233-55 - PubMed
  18. Int J Cancer. 2018 Jun 1;142(11):2363-2374 - PubMed
  19. Mol Cancer Ther. 2018 Jul;17(7):1494-1503 - PubMed
  20. Oncoimmunology. 2013 Dec 1;2(12):e26852 - PubMed
  21. Bioconjug Chem. 2018 Nov 21;29(11):3746-3756 - PubMed
  22. Cancer Res. 2001 Dec 15;61(24):8737-42 - PubMed
  23. J Immunol. 2003 Jan 15;170(2):805-15 - PubMed
  24. Trends Biotechnol. 1998 Dec;16(12):513-20 - PubMed
  25. J Cancer Res Clin Oncol. 2016 May;142(5):1003-11 - PubMed
  26. Semin Oncol. 1999 Oct;26(5 Suppl 14):58-65 - PubMed
  27. Protein Eng Des Sel. 2006 Jul;19(7):309-16 - PubMed
  28. Semin Oncol. 1999 Aug;26(4 Suppl 12):60-70 - PubMed
  29. Oncology. 2009;77(2):124-33 - PubMed
  30. Biotechnol Lett. 2016 Oct;38(10):1655-64 - PubMed
  31. Curr Protoc Protein Sci. 2013 Sep 24;73:30.1.1-30.1.16 - PubMed
  32. Bioconjug Chem. 2014 Apr 16;25(4):656-64 - PubMed
  33. Am J Pathol. 2018 Aug;188(8):1736-1743 - PubMed
  34. Chem Biol. 2008 Feb;15(2):128-36 - PubMed
  35. Mol Cell Biol. 2005 Sep;25(17):7734-42 - PubMed
  36. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320-4 - PubMed
  37. Bioconjug Chem. 2009 May 20;20(5):1010-5 - PubMed
  38. Mol Oncol. 2014 May;8(3):620-32 - PubMed
  39. Cancer Res. 2004 Mar 15;64(6):2120-6 - PubMed
  40. Cancer Immunol Immunother. 2015 Mar;64(3):287-97 - PubMed
  41. PLoS One. 2015 Mar 23;10(3):e0121989 - PubMed
  42. Methods Mol Biol. 2019;1904:1-10 - PubMed
  43. Oncotarget. 2019 Jan 25;10(8):897-915 - PubMed
  44. Cancer Treat Rev. 2018 Jan;62:39-49 - PubMed
  45. Cancer Res. 1984 Jan;44(1):259-64 - PubMed
  46. Eur J Radiol. 2012 Sep;81 Suppl 1:S124-6 - PubMed
  47. J Clin Pharmacol. 2017 Oct;57 Suppl 10:S11-S25 - PubMed
  48. Br J Haematol. 2018 Oct;183(2):313-317 - PubMed
  49. FEBS J. 2010 Dec;277(23):4814-27 - PubMed
  50. Chem Pharm Bull (Tokyo). 2019;67(3):173-185 - PubMed
  51. Curr Opin Immunol. 1999 Oct;11(5):548-57 - PubMed
  52. Oncotarget. 2016 May 24;7(21):29916-26 - PubMed
  53. Acta Pharmacol Sin. 2005 Jun;26(6):641-8 - PubMed
  54. Int J Biol Sci. 2019 Sep 7;15(12):2548-2560 - PubMed
  55. Clin Cancer Res. 1998 Oct;4(10):2545-50 - PubMed
  56. J Control Release. 2017 Jan 28;246:110-119 - PubMed
  57. Semin Oncol. 2002 Feb;29(1 Suppl 4):27-36 - PubMed
  58. Br J Cancer. 2013 Sep 17;109(6):1570-8 - PubMed
  59. Curr Gene Ther. 2010 Apr;10(2):77-90 - PubMed
  60. Cancer Biol Ther. 2016 Apr 2;17(4):346-54 - PubMed
  61. ACS Chem Biol. 2008 Jun 20;3(6):373-82 - PubMed
  62. Oncologist. 2007 May;12(5):577-83 - PubMed
  63. Cancer Chemother Pharmacol. 2017 Dec;80(6):1209-1217 - PubMed
  64. J Immunother. 2008 May;31(4):370-6 - PubMed
  65. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21-6 - PubMed
  66. J Photochem Photobiol B. 2009 Jul 17;96(1):1-8 - PubMed
  67. Chem Biol. 2003 Apr;10(4):313-7 - PubMed
  68. Expert Opin Biol Ther. 2003 Apr;3(2):305-18 - PubMed
  69. Oncotarget. 2016 Aug 23;7(34):54925-54936 - PubMed
  70. Onco Targets Ther. 2017 Jul 06;10:3313-3327 - PubMed
  71. Oncotarget. 2017 May 23;8(21):35069-35075 - PubMed
  72. Mediators Inflamm. 2015;2015:146282 - PubMed
  73. Bioconjug Chem. 1997 Jul-Aug;8(4):510-9 - PubMed
  74. Immunol Rev. 2016 Mar;270(1):152-64 - PubMed
  75. Nat Rev Cancer. 2010 Mar;10(3):194-204 - PubMed
  76. Curr Pharm Biotechnol. 2008 Dec;9(6):423-30 - PubMed
  77. PLoS One. 2013 Oct 25;8(10):e78745 - PubMed
  78. Nat Biotechnol. 2003 Jan;21(1):86-9 - PubMed
  79. Bioorg Med Chem Lett. 2014 Dec 1;24(23):5357-63 - PubMed
  80. Oncogene. 2007 May 14;26(22):3291-310 - PubMed
  81. Bioconjug Chem. 2013 Oct 16;24(10):1674-83 - PubMed
  82. Anticancer Drugs. 2017 Mar;28(3):263-270 - PubMed
  83. Breast Cancer Res. 2005;7(5):R617-26 - PubMed
  84. Oncotarget. 2016 Mar 22;7(12):14143-52 - PubMed
  85. Signal Transduct Target Ther. 2020 May 8;5(1):65 - PubMed
  86. Mol Cancer Ther. 2017 May;16(5):879-892 - PubMed
  87. Curr Biol. 2006 Jun 20;16(12):1194-200 - PubMed
  88. Immunol Rev. 2010 May;235(1):159-71 - PubMed
  89. Cancer Res. 1999 Mar 15;59(6):1236-43 - PubMed
  90. Acta Pharmacol Sin. 2005 Jan;26(1):1-9 - PubMed
  91. Pharmacol Rev. 2015 Oct;67(4):731-53 - PubMed
  92. Target Oncol. 2019 Feb;14(1):93-105 - PubMed
  93. Cancer Sci. 2009 Aug;100(8):1359-65 - PubMed
  94. Oncotarget. 2017 Jul 25;8(30):49671-49679 - PubMed
  95. Neuron. 1993 Jun;10(6):1089-99 - PubMed
  96. Immunol Today. 1983 Apr;4(4):100-1 - PubMed
  97. Curr Opin Chem Biol. 2009 Jun;13(3):235-44 - PubMed
  98. Trends Immunol. 2017 Aug;38(8):577-593 - PubMed
  99. Angew Chem Int Ed Engl. 2014 Apr 7;53(15):3796-827 - PubMed
  100. Bioconjug Chem. 2011 Dec 21;22(12):2487-95 - PubMed
  101. Int J Mol Sci. 2019 Dec 10;20(24): - PubMed
  102. BMC Cancer. 2012 Aug 08;12:345 - PubMed
  103. BMC Cancer. 2016 Jan 25;16:37 - PubMed
  104. MAbs. 2019 Feb/Mar;11(2):219-238 - PubMed
  105. Cancer Res. 2008 Nov 15;68(22):9280-90 - PubMed
  106. Trends Cell Biol. 2015 Jan;25(1):21-8 - PubMed
  107. Front Immunol. 2020 Jun 26;11:1261 - PubMed
  108. J Biol Chem. 1990 Nov 25;265(33):20678-85 - PubMed
  109. PLoS One. 2019 Oct 1;14(10):e0222280 - PubMed
  110. Curr Pharm Des. 2013;19(30):5406-13 - PubMed
  111. Oncoimmunology. 2014 Jan 1;3(1):e27048 - PubMed
  112. Leukemia. 2004 Feb;18(2):316-25 - PubMed
  113. Lancet. 2009 Mar 21;373(9668):1033-40 - PubMed
  114. Cancer J. 2008 May-Jun;14(3):154-69 - PubMed
  115. Front Pharmacol. 2017 Aug 23;8:561 - PubMed
  116. PLoS One. 2013;8(4):e61267 - PubMed
  117. Mol Oncol. 2013 Jun;7(3):475-83 - PubMed
  118. Nature. 1991 Jun 6;351(6326):501-2 - PubMed
  119. Int Rev Immunol. 2017 Jul 4;36(4):207-219 - PubMed
  120. J Immunother. 1999 Jan;22(1):41-7 - PubMed
  121. Int J Cancer. 2010 Sep 1;127(6):1453-61 - PubMed
  122. Adv Drug Deliv Rev. 2009 Sep 30;61(11):977-85 - PubMed
  123. Biologics. 2010 Aug 09;4:173-85 - PubMed
  124. J Biotechnol. 2007 May 1;129(3):539-46 - PubMed
  125. Biomol Ther (Seoul). 2015 Nov;23(6):493-509 - PubMed
  126. Ann Transl Med. 2018 Apr;6(8):143 - PubMed
  127. Chembiochem. 2005 Jul;6(7):1263-9 - PubMed
  128. Bioconjug Chem. 2015 Aug 19;26(8):1678-86 - PubMed
  129. Bioconjug Chem. 2017 May 17;28(5):1458-1469 - PubMed
  130. Int J Cancer. 2015 Sep 15;137(6):1457-66 - PubMed
  131. Front Biosci (Elite Ed). 2012 Jan 01;4:12-22 - PubMed
  132. PLoS One. 2015 Jul 01;10(7):e0131177 - PubMed
  133. J Clin Oncol. 2000 Apr;18(8):1622-36 - PubMed
  134. Nat Biotechnol. 1996 Jul;14(7):845-51 - PubMed
  135. Blood. 2009 Apr 16;113(16):3792-800 - PubMed
  136. Int J Oncol. 2003 Oct;23(4):1179-86 - PubMed
  137. J Clin Oncol. 2012 Sep 20;30(27):3330-6 - PubMed
  138. AAPS J. 2015 Sep;17(5):1055-64 - PubMed
  139. Expert Opin Biol Ther. 2008 Dec;8(12):1963-71 - PubMed
  140. Eur J Nucl Med Mol Imaging. 2010 Oct;37(10):1926-34 - PubMed
  141. Pharm Res. 2015 Nov;32(11):3480-93 - PubMed
  142. Oncology (Williston Park). 2009 May;23(6):488-96 - PubMed
  143. Cancer Res. 1987 Feb 1;47(3):707-12 - PubMed
  144. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8548-53 - PubMed
  145. Life Sci. 1999;64(16):1435-45 - PubMed
  146. Cancer Biol Ther. 2015;16(12):1764-74 - PubMed
  147. J Cancer Res Clin Oncol. 2015 Dec;141(12):2079-95 - PubMed
  148. Cancer Chemother Pharmacol. 2019 Jul;84(1):61-72 - PubMed
  149. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4285-9 - PubMed
  150. J Invest Dermatol. 2013 Jan;133(1):230-8 - PubMed
  151. J Biol Chem. 1991 Sep 15;266(26):17376-81 - PubMed
  152. Am J Clin Pathol. 2003 Apr;119(4):472-85 - PubMed
  153. Clin Ther. 2008 Jan;30(1):14-30 - PubMed
  154. Cancer Lett. 2016 Mar 28;372(2):201-9 - PubMed
  155. Clin Cancer Res. 2004 Oct 15;10(20):7063-70 - PubMed
  156. J Surg Res. 2015 Jul;197(1):5-11 - PubMed
  157. Cancer Chemother Pharmacol. 2019 Aug;84(2):327-336 - PubMed
  158. Biochem J. 2003 Oct 15;375(Pt 2):449-55 - PubMed
  159. Biochim Biophys Acta. 2016 Apr;1863(4):770-84 - PubMed
  160. Int J Oncol. 2009 Sep;35(3):547-57 - PubMed
  161. Pharm Res. 2015 Nov;32(11):3526-40 - PubMed
  162. Cancer Sci. 2016 Apr;107(4):486-90 - PubMed
  163. Cell Death Differ. 2006 Apr;13(4):576-85 - PubMed
  164. Curr Top Med Chem. 2018;18(3):192-198 - PubMed
  165. Clin Cancer Res. 2000 Jun;6(6):2157-65 - PubMed
  166. Mol Cancer Res. 2017 Sep;15(9):1153-1162 - PubMed
  167. PLoS Genet. 2013 Aug;9(8):e1003767 - PubMed
  168. Mol Cancer Ther. 2017 May;16(5):871-878 - PubMed
  169. Curr Opin Chem Biol. 2010 Aug;14(4):529-37 - PubMed
  170. Int J Cancer. 2000 Apr 15;86(2):269-75 - PubMed
  171. MAbs. 2016;8(3):617-52 - PubMed
  172. Mol Immunol. 1994 Feb;31(3):169-217 - PubMed
  173. Int J Cancer. 2016 Aug 15;139(4):916-27 - PubMed
  174. Cancer Res. 1992 May 1;52(9 Suppl):2747s-2751s - PubMed
  175. Biotechnol J. 2018 Feb;13(2): - PubMed
  176. Front Pharmacol. 2018 Oct 24;9:1208 - PubMed
  177. Protein Sci. 2016 Aug;25(8):1451-60 - PubMed
  178. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4538-42 - PubMed
  179. J Biol Chem. 1989 Sep 25;264(27):15953-9 - PubMed
  180. Eur J Cancer. 2011 Mar;47(5):773-83 - PubMed
  181. Immunol Today. 2000 Aug;21(8):397-402 - PubMed
  182. Cancer Genomics Proteomics. 2012 May-Jun;9(3):119-33 - PubMed
  183. Biochemistry. 1988 Sep 20;27(19):7263-8 - PubMed
  184. Int J Mol Sci. 2016 Apr 14;17(4):561 - PubMed
  185. Br J Haematol. 2014 Jan;164(2):251-7 - PubMed
  186. Nat Rev Cancer. 2012 Mar 22;12(4):278-87 - PubMed
  187. Biotechnol Genet Eng Rev. 2013;29:175-86 - PubMed
  188. Mol Cancer Ther. 2015 Jul;14(7):1614-24 - PubMed
  189. J Cell Mol Med. 2010 Apr;14(4):771-94 - PubMed
  190. PLoS One. 2012;7(3):e34003 - PubMed
  191. Monoclon Antib Immunodiagn Immunother. 2016 Jun;35(3):141-7 - PubMed
  192. J Exp Clin Cancer Res. 2018 Mar 16;37(1):61 - PubMed
  193. Curr Opin Investig Drugs. 2001 Sep;2(9):1282-93 - PubMed
  194. Lancet Oncol. 2019 Jun;20(6):816-826 - PubMed
  195. Cancer Lett. 2016 May 1;374(2):229-40 - PubMed
  196. Br J Cancer. 1997;75(11):1575-84 - PubMed
  197. Mol Cancer Ther. 2014 Sep;13(9):2194-202 - PubMed
  198. Nat Genet. 1997 Feb;15(2):146-56 - PubMed
  199. Clin Cancer Res. 2009 Feb 1;15(3):832-9 - PubMed
  200. Mol Cancer Ther. 2018 Jan;17(1):150-160 - PubMed
  201. Appl Microbiol Biotechnol. 1996 Dec;46(5-6):524-32 - PubMed
  202. N Engl J Med. 2004 Jul 22;351(4):337-45 - PubMed
  203. PLoS Med. 2005 Mar;2(3):e73 - PubMed
  204. Biochem Pharmacol. 1990 Oct 15;40(8):1859-64 - PubMed
  205. Cancer Res. 2016 May 1;76(9):2710-9 - PubMed
  206. Cancer Res. 1989 Jul 15;49(14):4062-7 - PubMed
  207. Bioconjug Chem. 2020 Jan 15;31(1):28-36 - PubMed
  208. Mol Cancer Ther. 2003 Dec;2(12):1341-50 - PubMed
  209. Nat Rev Drug Discov. 2004 Jul;3(7):549-50 - PubMed
  210. Oncologist. 2009 Mar;14(3):284-90 - PubMed
  211. Sci Rep. 2016 Jun 15;6:27871 - PubMed
  212. J Natl Cancer Inst. 1998 Jun 3;90(11):824-32 - PubMed
  213. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3980-4 - PubMed
  214. N Engl J Med. 2005 Nov 10;353(19):2012-24 - PubMed
  215. Lancet Oncol. 2019 Jun;20(6):827-836 - PubMed
  216. Mol Cancer Res. 2011 Apr;9(4):377-89 - PubMed
  217. Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):16-8 - PubMed
  218. Int J Cancer. 1995 Jan 3;60(1):137-44 - PubMed
  219. Mol Cancer Ther. 2015 May;14(5):1141-51 - PubMed
  220. Cancer Cell. 2009 Oct 6;16(4):347-58 - PubMed
  221. Biomedicines. 2018 Jun 20;6(2): - PubMed
  222. Cancer Res. 1986 Jul;46(7):3262-7 - PubMed
  223. Nat Rev Cancer. 2004 Apr;4(4):253-65 - PubMed
  224. Protein Eng Des Sel. 2006 Jul;19(7):299-307 - PubMed
  225. Clin Exp Vaccine Res. 2014 Jul;3(2):113-6 - PubMed
  226. Annu Rev Med. 2013;64:15-29 - PubMed
  227. J Cancer Res Clin Oncol. 2012 Jul;138(7):1081-90 - PubMed
  228. Biomedicines. 2017 Jun 28;5(3): - PubMed
  229. Cancer Res. 1985 Feb;45(2):879-85 - PubMed
  230. Annu Rev Med. 2018 Jan 29;69:191-207 - PubMed
  231. PLoS One. 2014 Nov 17;9(11):e113276 - PubMed
  232. Exp Cell Res. 2003 Mar 10;284(1):31-53 - PubMed
  233. Pharm Res. 2017 Apr;34(4):696-703 - PubMed
  234. Biomedicines. 2017 Feb 17;5(1): - PubMed
  235. J Clin Pharmacol. 2019 Sep;59(9):1225-1235 - PubMed
  236. Drug Resist Updat. 2015 Jan;18:36-46 - PubMed
  237. Cell Mol Life Sci. 2010 Sep;67(18):3197-208 - PubMed
  238. AAPS J. 2015 Mar;17(2):339-51 - PubMed
  239. Oncotarget. 2017 Jan 17;8(3):3980-4000 - PubMed

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