Display options
Cite
Balhorn R, Balhorn MC. Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers. Oncotarget. 2020;11(35):3315-3349doi: 10.18632/oncotarget.27709.
Balhorn, R., & Balhorn, M. C. (2020). Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers. Oncotarget, 11(35), 3315-3349. https://doi.org/10.18632/oncotarget.27709
Balhorn, Rod, and Balhorn, Monique Cosman. "Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers." Oncotarget vol. 11,35 (2020): 3315-3349. doi: https://doi.org/10.18632/oncotarget.27709
Balhorn R, Balhorn MC. Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers. Oncotarget. 2020 Sep 01;11(35):3315-3349. doi: 10.18632/oncotarget.27709. eCollection 2020 Sep 01. PMID: 32934776; PMCID: PMC7476732.
Copy Download .nbib Format: NLM
Share it on

Oncotarget. 2020 Sep 01;11(35):3315-3349. doi: 10.18632/oncotarget.27709. eCollection 2020 Sep 01.

Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers.

Oncotarget

Rod Balhorn, Monique Cosman Balhorn

Affiliations

  1. SHAL Technologies Inc., Livermore, CA 94550, USA.

PMID: 32934776 PMCID: PMC7476732 DOI: 10.18632/oncotarget.27709

Abstract

SH7139, the first of a series of selective high affinity ligand (SHAL) oncology drug candidates designed to target and bind to the HLA-DR proteins overexpressed by B-cell lymphomas, has demonstrated exceptional efficacy in the treatment of Burkitt lymphoma xenografts in mice and a safety profile that may prove to be unprecedented for an oncology drug. The aim of this study was to determine how frequently the HLA-DRs targeted by SH7139 are expressed by different subtypes of non-Hodgkin's lymphoma and by other solid cancers that have been reported to express HLA-DR. Binding studies conducted with SH7129, a biotinylated analog of SH7139, reveal that more than half of the biopsy sections obtained from patients with different types of non-Hodgkin's lymphoma express the HLA-DRs targeted by SH7139. Similar analyses of tumor biopsy tissue obtained from patients diagnosed with eighteen other solid cancers show the majority of these tumors also express the HLA-DRs targeted by SH7139. Cervical, ovarian, colorectal and prostate cancers expressed the most HLA-DR. Only a few esophageal and head and neck tumors bound the diagnostic. Within an individual's tumor, cell to cell differences in HLA-DR target expression varied by only 2 to 3-fold while the expression levels in tumors obtained from different patients varied as much as 10 to 100-fold. The high frequency with which SH7129 was observed to bind to these cancers suggests that many patients diagnosed with B-cell lymphomas, myelomas, and other non-hematological cancers should be considered potential candidates for new therapies such as SH7139 that target HLA-DR-expressing tumors.

Keywords: HLA-DR; SH7129; SH7139; selective high affinity ligand; solid cancers

Conflict of interest statement

CONFLICTS OF INTEREST R. Balhorn and M. Cosman Balhorn are co-founders and employees of SHAL Technologies Inc.

References

  1. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4163-70 - PubMed
  2. Am J Pathol. 1991 Aug;139(2):337-54 - PubMed
  3. World J Gastrointest Endosc. 2014 Aug 16;6(8):385-9 - PubMed
  4. Br J Urol. 1989 Mar;63(3):264-9 - PubMed
  5. Int J Cancer. 2008 Sep 15;123(6):1350-6 - PubMed
  6. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8581-5 - PubMed
  7. Int J Oncol. 2009 Feb;34(2):511-6 - PubMed
  8. Cancer Biother Radiopharm. 1998 Aug;13(4):239-54 - PubMed
  9. J Endocrinol Invest. 1990 Jan;13(1):41-8 - PubMed
  10. Leuk Lymphoma. 1991;6(1):31-8 - PubMed
  11. Int J Cancer. 2017 Feb 15;140(4):888-899 - PubMed
  12. Curr Opin Immunol. 1994 Oct;6(5):722-7 - PubMed
  13. J Pathol. 1994 Nov;174(3):183-9 - PubMed
  14. Blood. 1994 Apr 1;83(7):1760-8 - PubMed
  15. Neurologia. 2013 Apr;28(3):169-78 - PubMed
  16. Biomed Pharmacother. 2011 Sep;65(6):417-26 - PubMed
  17. Transplantation. 1992 Oct;54(4):639-44 - PubMed
  18. Breast Cancer Res. 2001;3(2):95-8 - PubMed
  19. Gastroenterol Jpn. 1990 Oct;25(5):575-84 - PubMed
  20. Science. 2015 Jan 23;347(6220):1260419 - PubMed
  21. AAPS J. 2015 May;17(3):535-45 - PubMed
  22. Hepatogastroenterology. 2001 Mar-Apr;48(38):458-61 - PubMed
  23. J Clin Invest. 1996 Dec 15;98(12):2819-26 - PubMed
  24. Cancer Biother Radiopharm. 2008 Dec;23(6):783-96 - PubMed
  25. Nature. 1991 Dec 5;354(6352):392-4 - PubMed
  26. J Immunol. 1995 Aug 1;155(3):1343-8 - PubMed
  27. Immunotherapy. 2017 Mar;9(4):361-371 - PubMed
  28. Int J Cancer. 2010 Jul 15;127(2):249-56 - PubMed
  29. J Natl Cancer Inst. 1995 Feb 15;87(4):280-5 - PubMed
  30. BJU Int. 2003 Mar;91(4):409-16 - PubMed
  31. J Immunol. 1983 Apr;130(4):1492-4 - PubMed
  32. J Exp Med. 1994 Jul 1;180(1):347-52 - PubMed
  33. Prostate. 1991;19(1):73-87 - PubMed
  34. APMIS. 1999 Apr;107(4):383-8 - PubMed
  35. Clin Cancer Res. 2012 Oct 15;18(20):5761-72 - PubMed
  36. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9461-5 - PubMed
  37. J Drug Target. 2020 Jul 2;:1-13 - PubMed
  38. J Natl Cancer Inst. 1985 Jun;74(6):1261-8 - PubMed
  39. Mol Immunol. 2008 Sep;45(15):3965-73 - PubMed
  40. N Engl J Med. 2002 Jun 20;346(25):1937-47 - PubMed
  41. J Clin Oncol. 1998 Oct;16(10):3246-56 - PubMed
  42. Oncogene. 2008 Oct 6;27(45):5932-43 - PubMed
  43. Cell Mol Immunol. 2004 Jun;1(3):180-5 - PubMed
  44. J Am Coll Cardiol. 2002 Aug 7;40(3):515-20 - PubMed
  45. Oncology. 1998 Jan-Feb;55(1):65-9 - PubMed
  46. Cancer Sci. 2006 Jan;97(1):57-63 - PubMed
  47. J Biol Chem. 2006 Oct 27;281(43):32676-83 - PubMed
  48. Science. 1995 Sep 1;269(5228):1281-4 - PubMed
  49. PLoS One. 2014 Jan 27;9(1):e87377 - PubMed
  50. J Biol Chem. 1996 Jun 14;271(24):13993-4000 - PubMed
  51. Haematologica. 2010 Jan;95(1):135-43 - PubMed
  52. Immunol Rev. 2006 Aug;212:8-27 - PubMed
  53. Am J Surg Pathol. 1999 Aug;23(8):970-6 - PubMed
  54. Br J Cancer. 2001 Nov 16;85(10):1527-34 - PubMed
  55. Nat Genet. 2003 Jan;33(1):49-54 - PubMed
  56. Br J Dermatol. 1986 Apr;114(4):465-72 - PubMed
  57. Arch Otolaryngol Head Neck Surg. 1990 Oct;116(10):1181-5 - PubMed
  58. Histol Histopathol. 2000 Jul;15(3):721-7 - PubMed
  59. Clin Exp Immunol. 2000 Mar;119(3):464-71 - PubMed
  60. Gut. 1986 Feb;27(2):153-7 - PubMed
  61. Eur Heart J. 1998 Oct;19(10):1564-72 - PubMed
  62. Clin Cancer Res. 2020 Jul 15;26(14):3694-3706 - PubMed
  63. Adv Immunol. 2007;96:41-101 - PubMed
  64. World J Gastroenterol. 2010 Jul 14;16(26):3258-66 - PubMed
  65. Annu Rev Pharmacol Toxicol. 2012;52:135-51 - PubMed
  66. J Virol. 2000 Jul;74(14):6632-6 - PubMed
  67. Cancer Res. 1993 Sep 1;53(17):3943-7 - PubMed
  68. Blood. 2015 Dec 10;126(24):2646-9 - PubMed
  69. Acta Derm Venereol Suppl (Stockh). 1981;94:1-40 - PubMed
  70. J Exp Med. 1985 Jan 1;161(1):98-112 - PubMed
  71. Science. 1999 May 21;284(5418):1351-4 - PubMed
  72. Prostate Cancer Prostatic Dis. 2008;11(4):334-41 - PubMed
  73. Gen Diagn Pathol. 1998 Apr;143(5-6):297-303 - PubMed
  74. Am J Clin Pathol. 1994 Jan;101(1):5-12 - PubMed
  75. ACS Chem Biol. 2007 Feb 20;2(2):119-27 - PubMed
  76. Immunol Rev. 2016 Mar;270(1):95-112 - PubMed
  77. N Engl J Med. 2005 Feb 3;352(5):441-9 - PubMed
  78. Blood. 2003 Feb 1;101(3):1038-44 - PubMed
  79. J Clin Endocrinol Metab. 1997 Sep;82(9):3136-40 - PubMed
  80. Neurosci Lett. 1987 Aug 18;79(1-2):195-200 - PubMed
  81. J Exp Med. 1984 Jun 1;159(6):1784-9 - PubMed
  82. Transplantation. 1990 May;49(5):991-5 - PubMed
  83. Lab Invest. 1992 Jan;66(1):96-107 - PubMed
  84. J Clin Oncol. 2014 Dec 20;32(36):4134-40 - PubMed
  85. J Exp Med. 1986 Oct 1;164(4):1013-28 - PubMed
  86. Clin Cancer Res. 2003 Aug 15;9(9):3260-71 - PubMed
  87. J Immunol. 2010 Oct 1;185(7):3809-13 - PubMed
  88. Clin Cancer Res. 2008 Dec 1;14(23):7667-73 - PubMed
  89. Cancer. 1994 Mar 1;73(5):1425-32 - PubMed
  90. J Proteomics. 2018 Mar 30;176:13-23 - PubMed
  91. Cancer Sci. 2011 Aug;102(8):1455-61 - PubMed
  92. Nat Rev Drug Discov. 2010 Apr;9(4):325-38 - PubMed
  93. J Exp Med. 1996 Mar 1;183(3):1185-92 - PubMed
  94. Cancer Res. 1999 Dec 15;59(24):6230-8 - PubMed
  95. Br J Cancer. 1993 Jul;68(1):80-5 - PubMed
  96. Blood. 2004 Nov 1;104(9):2635-42 - PubMed
  97. Anticancer Res. 2001 Jul-Aug;21(4A):2609-15 - PubMed
  98. Br J Cancer. 1996 Jan;73(2):148-53 - PubMed
  99. Am J Pathol. 2011 Feb;178(2):744-53 - PubMed
  100. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):251-7 - PubMed
  101. Thyroid. 1998 May;8(5):361-9 - PubMed
  102. Int J Cancer. 2005 Jun 10;115(2):231-40 - PubMed
  103. Br J Cancer. 1996 Mar;73(5):644-8 - PubMed
  104. J Exp Med. 1999 Mar 1;189(5):757-66 - PubMed
  105. Am Rev Respir Dis. 1989 Feb;139(2):330-4 - PubMed
  106. Mol Cancer. 2009 Apr 22;8:25 - PubMed
  107. J Immunol. 1994 Dec 15;153(12):5382-92 - PubMed
  108. Carcinogenesis. 2001 Oct;22(10):1615-23 - PubMed
  109. Mol Psychiatry. 2018 Feb;23(2):177-198 - PubMed
  110. Blood. 2010 Jun 24;115(25):5180-90 - PubMed
  111. Int J Cancer. 2005 Dec 10;117(5):807-15 - PubMed
  112. Leuk Lymphoma. 2004 Feb;45(2):345-9 - PubMed
  113. Mol Immunol. 1999 Aug;36(11-12):789-97 - PubMed
  114. Int J Cancer. 1987 Nov 15;40(5):598-603 - PubMed
  115. Br J Cancer. 2002 Sep 23;87(7):756-62 - PubMed
  116. Gastroenterology. 1991 Jan;100(1):3-12 - PubMed
  117. Surgery. 1994 Sep;116(3):510-5 - PubMed
  118. J Clin Pathol. 1991 Feb;44(2):107-14 - PubMed
  119. Exp Neurol. 1990 Oct;110(1):93-104 - PubMed
  120. J Clin Pathol. 1987 Aug;40(8):879-84 - PubMed
  121. J Immunol. 2003 Jun 15;170(12):6363-70 - PubMed
  122. J Immunol. 1999 Nov 15;163(10):5715-22 - PubMed
  123. J Immunol. 2000 Nov 15;165(10):5451-61 - PubMed
  124. J Breast Cancer. 2013 Dec;16(4):417-25 - PubMed
  125. Int J Clin Exp Pathol. 2015 May 01;8(5):5485-90 - PubMed
  126. Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9942-E9951 - PubMed
  127. Br J Cancer. 1988 Apr;57(4):369-73 - PubMed
  128. Cancer Res. 1988 Feb 15;48(4):1019-25 - PubMed
  129. Int J Cancer. 2006 Dec 15;119(12):2980-5 - PubMed
  130. Nat Commun. 2016 Jan 29;7:10582 - PubMed
  131. Leuk Lymphoma. 2007 May;48(5):944-56 - PubMed
  132. Tumori. 1991 Apr 30;77(2):122-5 - PubMed
  133. Transplantation. 1986 Jun;41(6):776-80 - PubMed
  134. Clin Cancer Res. 1997 Aug;3(8):1253-60 - PubMed
  135. Clin Exp Metastasis. 1990 Jul-Aug;8(4):319-28 - PubMed
  136. Gastric Cancer. 1998 Dec;1(1):71-77 - PubMed
  137. J Clin Endocrinol Metab. 1998 Jan;83(1):157-64 - PubMed
  138. Invest Ophthalmol Vis Sci. 2012 May 04;53(6):2640-6 - PubMed
  139. Blood. 2004 Jun 1;103(11):4251-8 - PubMed
  140. Oncol Lett. 2018 Nov;16(5):5655-5666 - PubMed
  141. Clin Cancer Res. 2005 Apr 1;11(7):2552-60 - PubMed
  142. Eur J Haematol. 2015 Jun;94(6):554-7 - PubMed
  143. Arch Pathol Lab Med. 1991 Oct;115(10):993-7 - PubMed
  144. J Clin Oncol. 2001 Feb 1;19(3):720-6 - PubMed
  145. Int Immunol. 2008 Aug;20(8):1057-66 - PubMed
  146. Int J Cancer Suppl. 1988;3:96-101 - PubMed
  147. Pancreas. 1990 Jul;5(4):415-20 - PubMed
  148. Cancer Res. 1987 Feb 1;47(3):830-40 - PubMed
  149. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3435-43 - PubMed
  150. Virchows Arch. 2005 Jan;446(1):10-4 - PubMed
  151. Clin Exp Immunol. 2007 Apr;148(1):127-35 - PubMed
  152. Blood. 1999 Oct 1;94(7):2217-24 - PubMed
  153. Leukemia. 1993 Mar;7(3):398-403 - PubMed
  154. Arch Neurol. 1991 Dec;48(12):1244-6 - PubMed
  155. Leukemia. 2002 Dec;16(12):2400-7 - PubMed
  156. Clin Exp Immunol. 1994 Aug;97(2):328-33 - PubMed
  157. Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):562-567 - PubMed
  158. Arthritis Rheum. 2010 Mar;62(3):667-73 - PubMed
  159. Pathol Res Pract. 1998;194(10):679-84 - PubMed
  160. Clin Cancer Res. 2007 Sep 1;13(17):5070-5 - PubMed
  161. Int J Oncol. 2015 Jan;46(1):324-32 - PubMed
  162. Tissue Antigens. 2008 Oct;72(4):321-34 - PubMed
  163. Clin Dev Immunol. 2003 Jun-Dec;10(2-4):213-26 - PubMed
  164. J Natl Cancer Inst. 1987 Nov;79(5):923-32 - PubMed
  165. J Clin Cell Immunol. 2015 Aug;6(4): - PubMed
  166. J Neuropathol Exp Neurol. 1990 Mar;49(2):122-36 - PubMed
  167. Clin Exp Immunol. 1986 Jul;65(1):165-71 - PubMed
  168. JCI Insight. 2018 Dec 20;3(24): - PubMed
  169. Anticancer Res. 1998 Jul-Aug;18(4B):2779-88 - PubMed
  170. Pediatr Blood Cancer. 2017 Dec;64(12): - PubMed
  171. J Allergy Clin Immunol. 1993 Sep;92(3):442-9 - PubMed
  172. PLoS One. 2017 Aug 17;12(8):e0182786 - PubMed
  173. Surgery. 1998 Sep;124(3):503-9 - PubMed
  174. J Immunol. 2009 Apr 1;182(7):4056-64 - PubMed
  175. Nat Rev Immunol. 2015 Apr;15(4):203-16 - PubMed
  176. Head Neck Oncol. 2013 Feb 27;5(3):24 - PubMed
  177. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3964-9 - PubMed
  178. J Immunol. 1998 Sep 15;161(6):2833-40 - PubMed
  179. Drug Metab Dispos. 2016 Oct;44(10):1550-61 - PubMed
  180. Clin Exp Immunol. 1991 May;84(2):303-7 - PubMed
  181. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;60(6):407-12 - PubMed
  182. J Neuroimmunol. 1989 Oct;24(3):173-82 - PubMed
  183. Eur J Immunogenet. 1998 Dec;25(6):385-91 - PubMed
  184. Int J Cancer. 2013 Dec 15;133(12):2895-902 - PubMed
  185. J Immunol. 2004 Apr 15;172(8):5095-102 - PubMed
  186. Int J Cancer Suppl. 1991;6:95-100 - PubMed
  187. J Immunol. 2001 Jul 1;167(1):147-55 - PubMed
  188. Drugs. 2003;63(8):803-43 - PubMed
  189. Cancer. 1990 Sep 15;66(6):1154-7 - PubMed
  190. Cancer Res. 2000 Apr 1;60(7):1921-6 - PubMed
  191. Cancer. 1997 Dec 15;80(12 Suppl):2706-11 - PubMed
  192. Blood. 2000 Nov 15;96(10):3569-77 - PubMed
  193. Lancet. 1984 Nov 3;2(8410):1009-13 - PubMed
  194. Vet Immunol Immunopathol. 2010 Oct 15;137(3-4):235-42 - PubMed
  195. J Nucl Med. 1999 Dec;40(12):2014-20 - PubMed
  196. Circ Res. 1990 Aug;67(2):360-7 - PubMed
  197. Open Cancer Immunol J. 2010 Jan 1;3:1-7 - PubMed
  198. Acta Oncol. 1994;33(2):187-90 - PubMed
  199. Clin Cancer Res. 2004 Aug 15;10(16):5327-34 - PubMed
  200. Am J Pathol. 1994 Aug;145(2):310-21 - PubMed
  201. Leuk Lymphoma. 2007 Mar;48(3):542-6 - PubMed
  202. Exp Oncol. 2008 Jun;30(2):96-101 - PubMed
  203. Cancer. 1949 Jul;2(4):635-42 - PubMed
  204. Blood. 1997 Sep 1;90(5):1960-7 - PubMed
  205. Mol Cancer Ther. 2018 Jan;17(1):150-160 - PubMed
  206. Am J Pathol. 2002 Jul;161(1):291-300 - PubMed
  207. Cancer Immunol Immunother. 2017 Jul;66(7):841-850 - PubMed
  208. Lancet Oncol. 2008 Feb;9(2):105-16 - PubMed
  209. Eur J Cancer. 2016 Nov;68:134-147 - PubMed
  210. BMC Cancer. 2012 Nov 27;12:561 - PubMed
  211. J Urol. 1996 Jan;155(1):361-7 - PubMed
  212. Adv Immunol. 2006;90:297-339 - PubMed
  213. Neoplasia. 2014 Jan;16(1):31-42 - PubMed
  214. Cancer. 1994 Jul 15;74(2):586-91 - PubMed
  215. Dig Dis Sci. 1988 Dec;33(12):1528-36 - PubMed
  216. J Immunol. 1995 Apr 15;154(8):3961-8 - PubMed
  217. J Exp Med. 1996 Dec 1;184(6):2207-16 - PubMed
  218. J Clin Oncol. 2006 Sep 1;24(25):4143-9 - PubMed
  219. Cancer Res. 2007 Apr 1;67(7):3269-75 - PubMed
  220. J Clin Invest. 1989 Feb;83(2):421-9 - PubMed
  221. Transplantation. 1989 Aug;48(2):238-43 - PubMed
  222. Am J Pathol. 1987 Jun;127(3):580-91 - PubMed
  223. Cells. 2017 Feb 10;6(1): - PubMed
  224. Cancer Res. 1992 Jul 15;52(14):4009-16 - PubMed
  225. Clin Exp Med. 2003 Sep;3(2):113-8 - PubMed
  226. Appl Immunohistochem Mol Morphol. 2001 Sep;9(3):234-41 - PubMed
  227. Oncology. 1998 Jul-Aug;55(4):326-33 - PubMed
  228. J BUON. 2002 Jul-Sep;7(3):207-16 - PubMed
  229. Eur J Immunol. 1994 Mar;24(3):759-64 - PubMed
  230. J Natl Cancer Inst. 1998 Feb 18;90(4):287-94 - PubMed
  231. Cancer Biol Ther. 2004 Oct;3(10):1021-7 - PubMed
  232. Nat Methods. 2012 Jul;9(7):671-5 - PubMed
  233. Annu Rev Immunol. 1993;11:571-611 - PubMed
  234. J Exp Med. 1994 Jul 1;180(1):35-42 - PubMed
  235. J Clin Pathol. 2000 Apr;53(4):286-91 - PubMed
  236. Cancer Biother Radiopharm. 2006 Dec;21(6):645-54 - PubMed
  237. Immunology. 1994 Aug;82(4):535-41 - PubMed
  238. Blood. 2006 Oct 15;108(8):2736-44 - PubMed
  239. Cancer Res. 2006 Jun 15;66(12):6387-94 - PubMed
  240. Cancer Immunol Res. 2016 May;4(5):390-9 - PubMed
  241. J Urol. 1993 Oct;150(4):1289-92 - PubMed
  242. PLoS One. 2014 Apr 01;9(4):e93231 - PubMed
  243. J Immunol. 2002 Jul 1;169(1):548-56 - PubMed
  244. J Hematol Oncol. 2014 Jun 12;7:44 - PubMed
  245. J Immunol. 2001 Jul 1;167(1):98-106 - PubMed
  246. J Exp Med. 1991 Jan 1;173(1):19-24 - PubMed
  247. J Clin Invest. 1988 Jul;82(1):370-2 - PubMed
  248. J Virol. 2007 Mar;81(6):2940-9 - PubMed
  249. J Autoimmun. 1990 Apr;3(2):187-200 - PubMed
  250. Int J Cancer. 2008 Feb 15;122(4):785-90 - PubMed
  251. Immunology. 1988 Dec;65(4):573-81 - PubMed
  252. Cancer Immunol Immunother. 2003 Jun;52(6):396-402 - PubMed
  253. Int J Breast Cancer. 2013;2013:250435 - PubMed

Publication Types