Kaposi's Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies.
BKV/Tat transgenic mice
HIV-1 tat
KS progression
KS regression
KS-like lesions
anti-Tat antibodies
inflammatory cytokines
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 Feb 2022
14 Feb 2022
Historique:
received:
22
12
2021
revised:
04
02
2022
accepted:
08
02
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
17
3
2022
Statut:
epublish
Résumé
Kaposi's sarcoma (KS) is an angioproliferative tumor showing an increased frequency and aggressiveness in HIV-infected subjects (AIDS-KS), due to the combined effects of inflammatory cytokines (IC), angiogenic factors, and the HIV-1 Tat protein. While the introduction of effective combined antiretroviral regimens greatly improved AIDS-KS incidence and course, it continues to be an incurable disease and the development of new rational targeted therapies is warranted. We used the BKV/Tat transgenic mouse model to evaluate the effects of IC and anti-Tat antibodies (Abs) treatment on KS-like lesions arising in BKV/Tat mice. We demonstrated here that IC-treatment increases the severity and delays the regression of KS-like lesions. Further, anti-Tat Abs reduced KS-like lesion severity developing in IC-treated mice when anti-Tat Abs were administered at an early-stage of lesion development as compared to more advanced lesions. Early anti-Tat Abs treatment also accelerated KS-like lesion regression and reduced the rate of severe-grade lesions. This effect was more evident in the first weeks after Ab treatment, suggesting that a longer treatment with anti-Tat Abs might be even more effective, particularly if administered just after lesion development. Although preliminary, these results are encouraging, and the approach deserves further studies for the development of anti-Tat Ab-based therapies for AIDS-KS. Clinical studies specifically addressing the effect of anti-Tat antibodies in treating AIDS-KS are not yet available. Nevertheless, the effectiveness of anti-Tat antibodies in controlling HIV/AIDS progression, likely due to the neutralization of extracellular Tat activities, is suggested by several cross-sectional and longitudinal clinical studies, indicating that anti-Tat Ab treatment or Tat-based vaccines may be effective to treat AIDS-KS patients or prevent the tumor in individuals at risk.
Identifiants
pubmed: 35216197
pii: ijms23042081
doi: 10.3390/ijms23042081
pmc: PMC8874961
pii:
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Anti-Retroviral Agents
0
Antibodies
0
Cytokines
0
tat Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero della Salute
ID : Role of HIV-1 and HHV-8 in Kaposi's sarcoma and AIDS-associated serous lymphomas
Références
Blood. 1998 Feb 1;91(3):956-67
pubmed: 9446657
PLoS One. 2013;8(1):e53145
pubmed: 23301033
Am J Pathol. 1996 Dec;149(6):1851-69
pubmed: 8952523
Blood. 1998 Feb 1;91(3):968-76
pubmed: 9446658
Nature. 1994 Oct 20;371(6499):674-80
pubmed: 7935812
J Virol. 1993 Jan;67(1):277-87
pubmed: 8416373
PLoS One. 2013 Sep 20;8(9):e74551
pubmed: 24073214
PLoS One. 2015 Jun 19;10(6):e0129425
pubmed: 26090662
HIV Med. 2018 May;19(5):355-364
pubmed: 29368388
AIDS. 2009 Feb 20;23(4):534-8
pubmed: 19169139
Retrovirology. 2013 Oct 28;10:123
pubmed: 24165011
Nucleic Acids Res. 2015 Oct 30;43(19):9362-78
pubmed: 26446987
J Virol. 2003 May;77(10):5759-73
pubmed: 12719569
Proc Natl Acad Sci U S A. 1995 May 23;92(11):4838-42
pubmed: 7539135
Cell. 2002 Feb 8;108(3):407-19
pubmed: 11853674
Nature. 1990 May 3;345(6270):84-6
pubmed: 2184372
Int J Cancer. 2011 Jan 1;128(1):82-93
pubmed: 20617515
J Virol. 2016 Jun 10;90(13):5886-5898
pubmed: 27053552
J Immunol. 1997 Feb 15;158(4):1887-94
pubmed: 9029130
Arch Virol. 2021 Nov;166(11):2955-2974
pubmed: 34390393
Am J Pathol. 1993 Jul;143(1):240-9
pubmed: 8100400
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7941-5
pubmed: 7690138
Blood. 1999 Jun 15;93(12):4044-58
pubmed: 10361101
AIDS. 1990 Jan;4(1):21-7
pubmed: 1969279
N Engl J Med. 1985 Dec 26;313(26):1659
pubmed: 4069179
Blood. 2003 Feb 15;101(4):1535-42
pubmed: 12393476
Am J Pathol. 1998 Jun;152(6):1433-43
pubmed: 9626048
Am J Pathol. 1999 Apr;154(4):1231-44
pubmed: 10233861
J Immunol. 1992 Dec 1;149(11):3727-34
pubmed: 1431144
Ann Intern Med. 1985 Nov;103(5):744-50
pubmed: 3901851
Nat Med. 2002 Mar;8(3):225-32
pubmed: 11875492
Cancer Res. 1993 Nov 15;53(22):5569-75
pubmed: 8221699
J Clin Invest. 1990 Jul;86(1):148-59
pubmed: 2114424
Arch Pathol Lab Med. 1988 Aug;112(8):825-8
pubmed: 3395219
Adv Cancer Res. 2001;81:161-200
pubmed: 11430595
Eur J Cancer. 2001 Jul;37(10):1251-69
pubmed: 11423257
Science. 1989 Jan 13;243(4888):223-6
pubmed: 2643161
Int J Mol Sci. 2020 Dec 30;22(1):
pubmed: 33396807
AIDS. 1996 Nov;10(13):1535-42
pubmed: 8931789
J Immunol. 1995 Apr 1;154(7):3582-92
pubmed: 7897237
PLoS One. 2016 Jan 29;11(1):e0147917
pubmed: 26824902
J Acquir Immune Defic Syndr (1988). 1989;2(2):158-62
pubmed: 2495349
Clin Exp Metastasis. 1999;17(7):575-82
pubmed: 10845556
AIDS. 1997 Oct;11(12):1421-31
pubmed: 9342064
J Immunol. 1999 Aug 15;163(4):1929-35
pubmed: 10438928
Neoplasia. 2009 Dec;11(12):1272-84
pubmed: 20019835
N Engl J Med. 1997 Apr 3;336(14):988-93
pubmed: 9077377
PLoS One. 2012;7(11):e48781
pubmed: 23152803
AIDS. 1998 Jan 1;12(1):19-27
pubmed: 9456251
Anal Quant Cytol Histol. 1991 Jun;13(3):201-8
pubmed: 1910421
Cancers (Basel). 2021 Dec 09;13(24):
pubmed: 34944828
Oncol Res Treat. 2017;40(3):94-98
pubmed: 28259888
Blood. 1999 Jul 15;94(2):663-72
pubmed: 10397733
J Virol. 2004 Sep;78(17):9336-42
pubmed: 15308728
Nat Rev Cancer. 2004 Nov;4(11):861-75
pubmed: 15516959
Clin Cancer Res. 1995 Mar;1(3):257-60
pubmed: 9815980
Nature. 1988 Oct 13;335(6191):606-11
pubmed: 2845275
AIDS. 1996 Sep;10(11):1211-9
pubmed: 8883582
Lancet. 1986 Dec 6;2(8519):1309-11
pubmed: 2878178
Clin Exp Immunol. 1989 Dec;78(3):329-33
pubmed: 2612049
Eur J Immunol. 1993 Sep;23(9):2375-8
pubmed: 8370415
Viral Immunol. 2014 Sep;27(7):356-60
pubmed: 25026101
J Virol. 2008 Dec;82(24):12126-44
pubmed: 18829766
J Clin Invest. 1995 Apr;95(4):1723-34
pubmed: 7535796
Expert Opin Pharmacother. 2011 Aug;12(11):1669-90
pubmed: 21517697
J Virol. 2014 Jun;88(12):6672-89
pubmed: 24696476
J Immunol. 1999 Jan 15;162(2):1165-70
pubmed: 9916748