Targeted human cytolytic fusion proteins at the cutting edge: harnessing the apoptosis-inducing properties of human enzymes for the selective elimination of tumor cells.

RNase-based hCFPs death-associated protein kinase (DAPk) granzyme B (GrB) microtubule-associated protein tau (MAPT tau) targeted human cytolytic fusion proteins (hCFPs)

Journal

Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965

Informations de publication

Date de publication:
25 Jan 2019
Historique:
received: 19 10 2018
accepted: 10 01 2019
entrez: 21 2 2019
pubmed: 21 2 2019
medline: 21 2 2019
Statut: epublish

Résumé

Patient-specific targeted therapy represents the holy grail of anti-cancer therapeutics, allowing potent tumor depletion without detrimental off-target toxicities. Disease-specific monoclonal antibodies have been employed to bind to oncogenic cell-surface receptors, representing the earliest form of immunotherapy. Targeted drug delivery was first achieved by means of antibody-drug conjugates, which exploit the differential expression of tumor-associated antigens as a guiding mechanism for the specific delivery of chemically-conjugated chemotherapeutic agents to diseased target cells. Biotechnological advances have expanded the repertoire of immunology-based tumor-targeting strategies, also paving the way for the next intuitive step in targeted drug delivery: the construction of recombinant protein drugs consisting of an antibody-based targeting domain genetically fused with a cytotoxic peptide, known as an immunotoxin. However, the most potent protein toxins have typically been derived from bacterial or plant virulence factors and commonly feature both off-target toxicity and immunogenicity in human patients. Further refinement of immunotoxin technology thus led to the replacement of monoclonal antibodies with humanized antibody derivatives, including the substitution of non-human toxic peptides with human cytolytic proteins. Preclinically tested human cytolytic fusion proteins (hCFPs) have proven promising as non-immunogenic combinatory anti-cancer agents, however they still require further enhancement to achieve convincing candidacy as a single-mode therapeutic. To date, a portfolio of highly potent human toxins has been established; ranging from microtubule-associated protein tau (MAP tau), RNases, granzyme B (GrB) and death-associated protein kinase (DAPk). In this review, we discuss the most recent findings on the use of these apoptosis-inducing hCFPs for the treatment of various cancers.

Identifiants

pubmed: 30783518
doi: 10.18632/oncotarget.26618
pii: 26618
pmc: PMC6368230
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

897-915

Déclaration de conflit d'intérêts

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Références

Life Sci. 1999;64(16):1435-45
pubmed: 10321723
Blood. 1999 Jun 15;93(12):4347-53
pubmed: 10361133
J Clin Invest. 1999 Jul;104(2):155-62
pubmed: 10411544
Curr Opin Immunol. 1999 Oct;11(5):584-8
pubmed: 10508711
Breast Cancer Res Treat. 1999 Jul;56(1):45-57
pubmed: 10517342
Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62
pubmed: 1057175
Protein Eng. 1999 Nov;12(11):1013-9
pubmed: 10585508
Cell. 2000 Jan 7;100(1):57-70
pubmed: 10647931
J Immunol Methods. 1999 Dec 10;231(1-2):159-67
pubmed: 10648935
J Cell Biochem. 2000 Jan;76(3):452-62
pubmed: 10649442
Cell Death Differ. 2000 Jan;7(1):17-24
pubmed: 10713717
J Clin Oncol. 2000 Apr;18(8):1622-36
pubmed: 10764422
Adv Drug Deliv Rev. 1998 Apr 6;31(1-2):53-88
pubmed: 10837618
Cytokine. 2000 Jun;12(6):786-90
pubmed: 10843765
Clin Cancer Res. 2000 Jun;6(6):2157-65
pubmed: 10873064
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8548-53
pubmed: 10890891
Cancer Treat Rev. 2000 Aug;26(4):269-86
pubmed: 10913382
Nature. 2000 Oct 12;407(6805):770-6
pubmed: 11048727
Cancer Res. 2001 Jan 1;61(1):249-55
pubmed: 11196170
EMBO J. 2001 Mar 1;20(5):1099-113
pubmed: 11230133
J Biol Chem. 2001 May 4;276(18):15177-84
pubmed: 11278311
Cancer Res. 2001 Apr 15;61(8):3225-9
pubmed: 11309270
Annu Rev Neurosci. 2001;24:1121-59
pubmed: 11520930
J Biol Chem. 2001 Dec 14;276(50):47460-7
pubmed: 11579085
Nature. 1975 Aug 7;256(5517):495-7
pubmed: 1172191
Genome Biol. 2001;2(12):REVIEWS3014
pubmed: 11790262
Oncogene. 2002 Feb 14;21(8):1217-24
pubmed: 11850841
J Cell Biol. 2002 Apr 29;157(3):455-68
pubmed: 11980920
Biochem Biophys Res Commun. 2002 Jun 7;294(2):287-92
pubmed: 12051708
J Cell Biol. 2002 Jun 24;157(7):1187-96
pubmed: 12082079
Cancer Cell. 2002 Feb;1(1):3-10
pubmed: 12086880
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14116-21
pubmed: 12381794
J Biol Chem. 2002 Dec 20;277(51):49523-30
pubmed: 12388539
Cancer Res. 2002 Nov 15;62(22):6634-8
pubmed: 12438260
Nat Rev Drug Discov. 2003 Jan;2(1):52-62
pubmed: 12509759
Cancer Immunol Immunother. 2003 May;52(5):338-41
pubmed: 12700949
Immunol Rev. 2003 Jun;193:31-8
pubmed: 12752668
Drug Resist Updat. 2003 Jun;6(3):111-27
pubmed: 12860459
Curr Opin Immunol. 2003 Oct;15(5):533-43
pubmed: 14499262
Postgrad Med J. 2003 Dec;79(938):672-80
pubmed: 14707241
Mol Cancer Ther. 2003 Dec;2(12):1341-50
pubmed: 14707275
Cell Death Differ. 2004 Apr;11(4):369-71
pubmed: 14726962
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):13-5
pubmed: 14734445
N Engl J Med. 2004 Mar 11;350(11):1079-80
pubmed: 15014180
FEBS Lett. 2004 Mar 26;562(1-3):87-92
pubmed: 15044006
Nat Rev Cancer. 2004 Apr;4(4):253-65
pubmed: 15057285
Semin Cancer Biol. 2004 Aug;14(4):283-94
pubmed: 15219621
Cancer Res. 2004 Jul 15;64(14):4870-4
pubmed: 15256457
Mol Cell Biol. 2004 Oct;24(19):8611-26
pubmed: 15367680
Blood. 2005 Mar 1;105(5):2049-58
pubmed: 15528317
Q J Nucl Med Mol Imaging. 2004 Dec;48(4):251-7
pubmed: 15640788
J Immunother. 2005 May-Jun;28(3):245-51
pubmed: 15838381
Mol Cell Biol. 2005 Sep;25(17):7854-67
pubmed: 16107729
Prog Nucleic Acid Res Mol Biol. 2005;80:349-74
pubmed: 16164979
Cell Death Differ. 2006 Apr;13(4):576-85
pubmed: 16179940
Trends Cell Biol. 2006 Feb;16(2):88-96
pubmed: 16406522
Curr Drug Targets. 2006 Mar;7(3):305-26
pubmed: 16515529
Annu Rev Biochem. 2006;75:189-210
pubmed: 16756490
Curr Biol. 2006 Jun 20;16(12):1194-200
pubmed: 16782009
Mol Biosyst. 2005 Oct;1(4):294-302
pubmed: 16880994
Future Oncol. 2006 Aug;2(4):493-508
pubmed: 16922616
J Pain. 2006 Sep;7(9):626-34
pubmed: 16942948
Autophagy. 2006 Apr-Jun;2(2):74-9
pubmed: 17139808
J Immunol. 2006 Dec 15;177(12):8822-34
pubmed: 17142785
J Cell Sci. 2006 Dec 15;119(Pt 24):5011-4
pubmed: 17158907
J Exp Med. 1992 Feb 1;175(2):553-66
pubmed: 1732416
Expert Opin Ther Targets. 2007 Oct;11(10):1299-314
pubmed: 17907960
Cell Death Differ. 2008 Apr;15(4):762-72
pubmed: 18202702
Blood. 2008 Apr 1;111(7):3830-7
pubmed: 18230757
Annu Rev Immunol. 2008;26:389-420
pubmed: 18304003
J Immunother. 2008 May;31(4):370-6
pubmed: 18391759
Leuk Lymphoma. 2008 Jul;49(7):1368-73
pubmed: 18452062
Curr Pharm Biotechnol. 2008 Jun;9(3):210-4
pubmed: 18673286
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13799-804
pubmed: 18772390
Mol Cancer Ther. 2008 Sep;7(9):2924-32
pubmed: 18790773
Nat Rev Mol Cell Biol. 2008 Nov;9(11):910-6
pubmed: 18813291
Expert Opin Biol Ther. 2009 Jan;9(1):79-95
pubmed: 19063695
Curr Pharm Biotechnol. 2008 Dec;9(6):423-30
pubmed: 19075682
Clin Cancer Res. 2009 Feb 1;15(3):832-9
pubmed: 19188153
J Cell Biol. 2009 Apr 6;185(1):35-42
pubmed: 19332886
Biochemistry. 2009 May 12;48(18):3804-6
pubmed: 19354288
Curr Opin Chem Biol. 2009 Jun;13(3):235-44
pubmed: 19414278
J Immunother. 2009 Jun;32(5):431-41
pubmed: 19609235
Adv Drug Deliv Rev. 2009 Sep 30;61(11):977-85
pubmed: 19679153
Curr Pharm Des. 2009;15(23):2676-92
pubmed: 19689338
Curr Pharm Des. 2009;15(23):2693-9
pubmed: 19689339
Cancer Cell. 2009 Oct 6;16(4):347-58
pubmed: 19800579
FEBS J. 2010 Jan;277(1):74-80
pubmed: 19878310
FEBS J. 2010 Jan;277(1):47
pubmed: 19878314
Cell Death Differ. 2010 Apr;17(4):616-23
pubmed: 20075940
BMC Cancer. 2010 Feb 05;10:34
pubmed: 20137089
Nat Rev Cancer. 2010 Mar;10(3):194-204
pubmed: 20147901
Curr Opin Immunol. 2010 Jun;22(3):308-13
pubmed: 20226643
Curr Opin Chem Biol. 2010 Aug;14(4):529-37
pubmed: 20643572
PLoS One. 2010 Nov 30;5(11):e14120
pubmed: 21152427
Theranostics. 2011 Feb 17;1:189-200
pubmed: 21547159
Mol Cell. 2011 Aug 19;43(4):613-23
pubmed: 21855800
Mol Cancer Ther. 2012 Jan;11(1):143-53
pubmed: 22090420
Mol Pharm. 2012 Mar 5;9(3):458-69
pubmed: 22206488
J Control Release. 2012 Jul 20;161(2):422-8
pubmed: 22306430
J Clin Oncol. 2012 May 20;30(15):1822-8
pubmed: 22355053
Cancer Res. 2012 Jul 15;72(14):3631-41
pubmed: 22593189
Cancer Genomics Proteomics. 2012 May-Jun;9(3):119-33
pubmed: 22593247
Proteins. 2012 Nov;80(11):2514-22
pubmed: 22733450
Bioconjug Chem. 2012 Aug 15;23(8):1567-76
pubmed: 22759275
Annu Rev Med. 2013;64:15-29
pubmed: 23043493
Curr Med Res Opin. 2013 Apr;29(4):405-14
pubmed: 23402224
Blood Cancer J. 2013 Mar 22;3:e106
pubmed: 23524591
PLoS One. 2013;8(4):e61267
pubmed: 23573299
Nat Rev Drug Discov. 2013 May;12(5):329-32
pubmed: 23629491
Chromosoma. 2013 Oct;122(5):431-49
pubmed: 23775312
Int J Mol Sci. 2013 Jul 04;14(7):13858-72
pubmed: 23880846
Br J Cancer. 2013 Sep 17;109(6):1570-8
pubmed: 23942071
Sci Transl Med. 2013 Oct 23;5(208):208ra147
pubmed: 24154601
Br J Haematol. 2014 Jan;164(2):251-7
pubmed: 24164493
Apoptosis. 2014 Feb;19(2):298-305
pubmed: 24217921
Apoptosis. 2014 Feb;19(2):286-97
pubmed: 24220854
Biochemistry. 1986 Jun 17;25(12):3527-32
pubmed: 2424496
Apoptosis. 2014 Feb;19(2):371-86
pubmed: 24305735
J Invest Dermatol. 2014 Feb;134(2):1-5
pubmed: 24424458
J Immunol. 1987 Nov 15;139(10):3184-8
pubmed: 2445811
Angew Chem Int Ed Engl. 2014 Apr 7;53(15):3796-827
pubmed: 24677743
Biochemistry. 1989 Sep 5;28(18):7401-8
pubmed: 2479414
Oncogene. 2015 Apr 16;34(16):2138-2144
pubmed: 24909167
Cell Death Differ. 2014 Sep;21(9):1350-64
pubmed: 24948009
Biochemistry. 1989 Feb 21;28(4):1726-32
pubmed: 2497770
Mol Cancer Ther. 2014 Sep;13(9):2194-202
pubmed: 24980949
Mol Cell Biol. 2014 Nov;34(21):4033-48
pubmed: 25135476
Trends Cell Biol. 2015 Jan;25(1):21-8
pubmed: 25220181
AAPS J. 2015 Mar;17(2):339-51
pubmed: 25604608
J Clin Invest. 2015 Feb;125(2):487-9
pubmed: 25642709
J Immunother. 2015 Apr;38(3):85-95
pubmed: 25710248
Cancer Lett. 2015 Sep 1;365(2):149-55
pubmed: 25888452
Eur J Oncol Nurs. 2015 Dec;19(6):597-603
pubmed: 26088125
Biol Res. 2015 Sep 12;48:50
pubmed: 26363785
Cancer Immunol Immunother. 2015 Dec;64(12):1575-86
pubmed: 26472728
Mediators Inflamm. 2015;2015:146282
pubmed: 26491220
Immunol Cell Biol. 2016 May;94(5):470-8
pubmed: 26743033
Cancer Lett. 2016 Mar 28;372(2):201-9
pubmed: 26806809
Mol Cancer Ther. 2016 May;15(5):971-84
pubmed: 26826117
Cancer Lett. 2016 May 1;374(2):229-40
pubmed: 26912070
Int J Cancer. 2016 Aug 15;139(4):916-27
pubmed: 27037627
Protein Sci. 2016 Aug;25(8):1451-60
pubmed: 27110669
Toxins (Basel). 2016 Jul 01;8(7):
pubmed: 27376327
Front Mol Neurosci. 2016 Jun 23;9:46
pubmed: 27445685
Oncotarget. 2016 Oct 11;7(41):67166-67174
pubmed: 27564103
Cancer Res. 1989 Jul 15;49(14):4062-7
pubmed: 2786751
Oncotarget. 2016 Dec 27;7(52):87016-87030
pubmed: 27894092
Biomedicines. 2017 Feb 17;5(1):
pubmed: 28536352
Nat Rev Cancer. 2017 May 24;17(6):352-366
pubmed: 28536452
Biomedicines. 2017 Jun 28;5(3):
pubmed: 28657611
J Biol Chem. 1987 Jun 25;262(18):8707-11
pubmed: 2885323
Blood. 2017 Dec 21;130(25):2709-2717
pubmed: 28974506
Blood. 2018 May 24;131(21):2331-2334
pubmed: 29487070
Biomedicines. 2018 Mar 05;6(1):null
pubmed: 29510557
Am J Pathol. 2018 Aug;188(8):1736-1743
pubmed: 29870741
Leukemia. 2018 Aug;32(8):1768-1777
pubmed: 30030507
Drug Des Devel Ther. 2018 Jul 24;12:2293-2300
pubmed: 30087554
Onco Targets Ther. 2018 Aug 06;11:4583-4590
pubmed: 30122950
BMC Cancer. 2018 Nov 15;18(1):1117
pubmed: 30442119
J Cell Physiol. 2019 May;234(5):5628-5642
pubmed: 30478951
Onco Targets Ther. 2018 Nov 22;11:8265-8272
pubmed: 30538495
Proc Natl Acad Sci U S A. 1987 Apr;84(8):2238-41
pubmed: 3470787
Cancer Drug Deliv. 1987;4(4):245-53
pubmed: 3502618
Science. 1986 May 16;232(4752):858-61
pubmed: 3518058
Biochemistry. 1985 Sep 24;24(20):5480-6
pubmed: 4074709
J Mol Biol. 1977 Oct 25;116(2):207-25
pubmed: 599557
Nat Struct Biol. 1995 May;2(5):350-4
pubmed: 7664088
J Immunol. 1995 Jun 15;154(12):6299-305
pubmed: 7759868
Genes Dev. 1995 Jan 1;9(1):15-30
pubmed: 7828849
J Exp Med. 1995 Mar 1;181(3):1037-46
pubmed: 7869027
J Biol Chem. 1994 Oct 28;269(43):26739-45
pubmed: 7929408
Adv Immunol. 1994;56:301-87
pubmed: 8073950
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1677-81
pubmed: 8127865
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2920-4
pubmed: 8159680
J Biol Chem. 1994 Jun 10;269(23):15957-60
pubmed: 8206889
Neuron. 1993 Jun;10(6):1089-99
pubmed: 8318230
EMBO J. 1996 May 15;15(10):2407-16
pubmed: 8665848
Sci Am. 1996 Sep;275(3):80-7
pubmed: 8701297
Appl Microbiol Biotechnol. 1996 Dec;46(5-6):524-32
pubmed: 9008885
Leukemia. 1997 Feb;11(2):253-7
pubmed: 9009089
J Biol Chem. 1997 Jul 18;272(29):17907-11
pubmed: 9218414
Immunotechnology. 1997 Jun;3(2):127-36
pubmed: 9237097
Oncogene. 1997 Jul 24;15(4):403-7
pubmed: 9242376
Immunity. 1998 Apr;8(4):451-60
pubmed: 9586635
J Immunother. 1999 Jan;22(1):41-7
pubmed: 9924698

Auteurs

Neelakshi Mungra (N)

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Sandra Jordaan (S)

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Precious Hlongwane (P)

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Krupa Naran (K)

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Shivan Chetty (S)

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Stefan Barth (S)

Medical Biotechnology and Immunotherapy Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.

Classifications MeSH