title: Immunotoxins: the role of the toxin.
abstract: Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular toxin action to kill target cells. Target specificity is determined via the binding attributes of the chosen antibody. Mostly, but not exclusively, immunotoxins are purpose-built to kill cancer cells as part of novel treatment approaches. Other applications for immunotoxins include immune regulation and the treatment of viral or parasitic diseases. Here we discuss the utility of protein toxins, of both bacterial and plant origin, joined to antibodies for targeting cancer cells. Finally, while clinical goals are focused on the development of novel cancer treatments, much has been learned about toxin action and intracellular pathways. Thus toxins are considered both medicines for treating human disease and probes of cellular function.
authors: Biotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, 37 Convent Dr, Bethesda, MD 20892, USA. antignaa@mail.nih.gov
authors: Antonella
authors: A
authors: Antignani
authors: David
authors: D
authors: Fitzgerald
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins
references: J Biol Chem. 1993 Feb 15;268(5):3514-9
references: 8429026
references: Clin Cancer Res. 2000 Apr;6(4):1302-13
references: 10778955
references: Cell. 1986 Dec 5;47(5):641-8
references: 3536124
references: Clin Cancer Res. 2011 Sep 15;17(18):5926-34
references: 21813632
references: Proc Natl Acad Sci U S A. 1990 Jan;87(1):308-12
references: 2104981
references: Curr Pharm Biotechnol. 2008 Jun;9(3):153-60
references: 18673280
references: Cell Mol Life Sci. 2006 Aug;63(16):1850-66
references: 16799768
references: Nature. 1975 Aug 7;256(5517):495-7
references: 1172191
references: Toxins (Basel). 2010 Nov;2(11):2519-83
references: 22069564
references: Clin Cancer Res. 1998 Nov;4(11):2599-604
references: 9829722
references: PLoS Pathog. 2010 Jun 10;6(6):e1000803
references: 20548940
references: Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5742-7
references: 21436054
references: FEBS Lett. 2002 Oct 2;529(1):49-53
references: 12354612
references: Cancer Res. 2010 Feb 1;70(3):1082-9
references: 20103626
references: Immunol Rev. 1982;62:159-83
references: 7042537
references: J Clin Oncol. 1989 Dec;7(12):1932-42
references: 2685183
references: N Engl J Med. 2001 Jul 26;345(4):241-7
references: 11474661
references: J Clin Oncol. 2012 May 20;30(15):1822-8
references: 22355053
references: Science. 1983 Feb 11;219(4585):644-50
references: 6218613
references: Science. 1988 Oct 21;242(4877):423-6
references: 3140379
references: Cell. 1985 Jul;41(3):653-4
references: 3891095
references: Mol Cancer Ther. 2010 Jul;9(7):2007-15
references: 20587662
references: Blood. 1990 Nov 1;76(9):1723-33
references: 2224122
references: Science. 1991 Nov 22;254(5035):1173-7
references: 1683495
references: J Biol Chem. 1989 Sep 5;264(25):14653-61
references: 2475487
references: Cancer Res. 2011 Oct 15;71(20):6300-9
references: 21998010
references: Toxicon. 2010 Sep 1;56(3):313-23
references: 20350563
references: Proc Natl Acad Sci U S A. 2012 May 1;109(18):6898-903
references: 22509046
references: J Clin Oncol. 2001 Jan 15;19(2):376-88
references: 11208829
references: Semin Cell Biol. 1991 Feb;2(1):31-7
references: 1954341
references: Neuro Oncol. 2010 Aug;12(8):871-81
references: 20511192
references: Toxicon. 2004 Sep 15;44(4):371-83
references: 15302521
references: Curr Top Microbiol Immunol. 1998;234:63-81
references: 9670613
references: Proc Natl Acad Sci U S A. 1990 Nov;87(22):8889-93
references: 1701055
references: J Biol Chem. 1995 Nov 24;270(47):28037-41
references: 7499288
references: J Immunother. 2008 Feb-Mar;31(2):189-98
references: 18481388
references: J Biomol Screen. 2011 Apr;16(4):436-42
references: 21364088
references: Br J Haematol. 2011 Aug;154(4):471-6
references: 21732928
references: J Clin Invest. 1984 Sep;74(3):966-71
references: 6432853
references: Biochemistry. 1994 May 10;33(18):5451-9
references: 7910034
references: Curr Opin Cell Biol. 2006 Dec;18(6):685-9
references: 17046225
references: Cancer Res. 1991 Aug 1;51(15):4052-8
references: 1855219
references: Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11782-7
references: 22753489
references: Clin Cancer Res. 2010 Mar 15;16(6):1894-903
references: 20215554
references: Cancer Res. 2008 Aug 1;68(15):6300-5
references: 18676854
references: J Clin Oncol. 1997 Feb;15(2):723-34
references: 9053498
references: Clin Cancer Res. 2007 Sep 1;13(17):5144-9
references: 17785569
references: Transplantation. 2002 May 27;73(10):1658-66
references: 12042656
references: J Biol Chem. 1989 Oct 25;264(30):17739-44
references: 2808346
references: Blood. 1988 Oct;72(4):1197-202
references: 3262384
references: Semin Immunol. 1990 Nov;2(6):467-79
references: 2104283
references: Clin Cancer Res. 2006 Aug 1;12(15):4695-701
references: 16899620
references: J Biomed Res. 2011 Mar;25(2):148-54
references: 23554683
references: Prog Clin Biol Res. 1979;31:751-9
references: 119972
references: J Immunol Methods. 1996 Oct 16;197(1-2):69-83
references: 8890895
references: FASEB J. 1994 Feb;8(2):201-8
references: 8119491
references: Proc Natl Acad Sci U S A. 1988 Aug;85(16):5879-83
references: 3045807
references: J Cell Biol. 1980 Dec;87(3 Pt 1):828-32
references: 7462324
references: Neurosurgery. 1997 Nov;41(5):1039-49; discussion 1049-51
references: 9361057
references: Eur J Immunol. 1976 Jul;6(7):511-9
references: 825377
references: J Biol Chem. 1990 Nov 25;265(33):20678-85
references: 2122978
references: Infect Immun. 1995 Jan;63(1):82-7
references: 7806387
references: Annu Rev Biochem. 1992;61:331-54
references: 1497314
references: Biochemistry. 1999 Dec 14;38(50):16507-13
references: 10600112
references: Blood. 1985 Sep;66(3):627-35
references: 3896347
references: Leuk Lymphoma. 2011 Apr;52(4):587-96
references: 21275630
references: Cancer Res. 1985 Mar;45(3):1005-7
references: 2982480
references: Blood. 2009 Apr 16;113(16):3792-800
references: 18988862
references: J Immunol. 1986 Apr 15;136(8):3103-9
references: 3958490
references: J Clin Oncol. 2009 Jun 20;27(18):2983-90
references: 19414673
references: J Biol Chem. 1993 Nov 15;268(32):23986-90
references: 8226941
references: Dev Cell. 2011 Aug 16;21(2):231-44
references: 21782526
references: J Biol Chem. 1995 Aug 25;270(34):20078-83
references: 7650025
references: Cancer Res. 2013 Apr 1;73(7):2281-8
references: 23348423
references: J Cell Biol. 1980 Dec;87(3 Pt 1):849-54
references: 7462326
references: Immunol Rev. 1982;62:75-91
references: 7042541
references: Annu Rev Med. 2007;58:221-37
references: 17059365
references: Nat Rev Cancer. 2006 Jul;6(7):559-65
references: 16794638
references: Anal Biochem. 1992 Sep;205(2):263-70
references: 1332541
references: Biol Blood Marrow Transplant. 2004 Aug;10(8):552-60
references: 15282533
references: Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7538-42
references: 8356052
references: J Neurosurg. 1994 Mar;80(3):520-6
references: 8113865
references: J Bacteriol. 1965 Dec;90(6):1557-62
references: 5854584
references: Blood. 1985 Feb;65(2):289-97
references: 3871341
references: Int J Cancer. 2013 Feb 15;132(4):978-87
references: 22821746
references: Clin Cancer Res. 2002 Oct;8(10):3092-9
references: 12374676
references: Nature. 1989 Jun 1;339(6223):394-7
references: 2498664
references: Blood. 1985 Oct;66(4):908-12
references: 3929860
references: J Immunol. 2007 Oct 1;179(7):4919-28
references: 17878392
references: J Clin Oncol. 2005 Sep 20;23(27):6719-29
references: 16061911
references: Nature. 1981 Mar 12;290(5802):145-6
references: 7207595
references: J Cell Biol. 1994 May;125(4):743-53
references: 8188744
references: Biochemistry. 1994 Sep 20;33(37):11254-63
references: 7537085
references: Mol Med. 1998 Jun;4(6):384-91
references: 10780881
references: J Pediatr Hematol Oncol. 2009 Dec;31(12):936-41
references: 19875969
references: Neurosurg Focus. 2006 Apr 15;20(4):E15
references: 16709020
references: Int J Cancer. 1989 Feb 15;43(2):215-9
references: 2465276
references: J Cell Biol. 2003 Mar 31;160(7):1139-50
references: 12668662
references: Blood. 1996 Aug 1;88(3):824-30
references: 8704237
references: Int J Med Microbiol. 2000 Oct;290(4-5):415-20
references: 11111920
references: Cancer Res. 1987 Nov 15;47(22):5924-31
references: 3499221
references: PLoS One. 2011;6(9):e24012
references: 21915275
references: Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3075-9
references: 1557415
references: Cancer Treat Res. 1988;37:371-89
references: 2908633
references: Leuk Lymphoma. 2011 Jun;52 Suppl 2:79-81
references: 21599608
references: Nature. 1978 Feb 23;271(5647):752-5
references: 625344
references: Bone Marrow Transplant. 1991 Aug;8(2):135-42
references: 1933055
references: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17099-104
references: 17940013
references: Br J Haematol. 1998 Jul;102(2):509-15
references: 9695966
references: Cell. 1978 Sep;15(1):245-50
references: 699044
references: FEBS J. 2011 Dec;278(23):4683-700
references: 21585657