Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector

被引：20

作者：

Batchu, Ramesh B. ^{[1
,2
]}

Gruzdyn, Oksana V. ^{[1
,2
]}

Moreno-Bost, AMberly M. ^{[4
]}

Szmania, Susann ^{[7
]}

Jayandharan, Giridhararao ^{[5
]}

Srivastava, Arun ^{[5
]}

Kolli, Bala K. ^{[6
]}

Weaver, Donald W. ^{[1
,3
]}

van Rhee, Frits ^{[7
]}

Gruber, Scott A. ^{[1
,2
]}

机构：

[1] Wayne State Univ, Dept Surg, Lab Surg Oncol & Dev Therapeut, Detroit, MI 48201 USA

[2] John D Dingell VA Med Ctr, Detroit, MI USA

[3] Virocan Therapeut Pvt Ltd, Hyderabad, Andhra Pradesh, India

[4] Arkansas CLIA Lab, Little Rock, AR USA

[5] Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL USA

[6] Rosalind Franklin Univ Med & Sci, N Chicago, IL USA

[7] UAMS, Winthrop P Rockefeller Canc Inst, Little Rock, AR USA

来源：

VACCINE | 2014年 / 32卷 / 08期

关键词：

Epithelial ovarian cancer; MAGE-A3; Adeno-associated Virus 6; Capsid tyrosine mutant; Dendritic cells; Cytotoxic T lymphocytes; DENDRITIC CELLS; MULTIPLE-MYELOMA; GENE-THERAPY; IN-VITRO; TRANSDUCTION; EXPRESSION; MAGE; IMMUNOTHERAPY; PROGNOSIS; NY-ESO-1;

D O I：

10.1016/j.vaccine.2013.12.049

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

MAGE-A3 is highly expressed in epithelial ovarian cancer (EOC), making it a promising candidate for immunotherapy. We investigated whether dendritic cells (DCs) transduced with a rAAV-6 capsid mutant vector Y445F could elicit effective MAGE-A3-specific anti-tumor cytotoxic T lymphocyte (CTL) responses in vitro. MAGE-A3 was cloned and rAAV-6-MAGE-A3 purified, followed by proviral genome detection using real-time PCR. Immunofluorescence detection of rAAV-6-Y445F-MAGE-A3-transduced DCs demonstrated 60% transduction efficiency. Fluorescent in situ hybridization analysis confirmed chromosomal integration of rAAV vectors. Flow cytometric analysis of transduced DCs showed unaltered expression of critical monocyte-derived surface molecules with retention of allo-stimulatory activity. Co-culture of autologous T lymphocytes with MAGE-A3-expressing DCs produced CTLs that secreted IFIN-gamma, and efficiently killed MAGE-A3+ EOC cells. This form of rAAV-based DC immunotherapy, either alone or more likely in combination with other immune-enhancing protocols, may prove useful in the clinical setting for management of EOC. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：938 / 943

页数：6

共 42 条

[1] Treatment of ovarian cancer cell lines with 5-aza-2'-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules [J].

Adair, Sara J. ;

Hogan, Kevin T. .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2009, 58 (04) :589-601

[2] Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands [J].

Aldrich, WA ;

Ren, C ;

White, AF ;

Zhou, SZ ;

Kumar, S ;

Jenkins, CB ;

Shaw, DR ;

Strong, TV ;

Triozzi, PL ;

Ponnazhagan, S .

GENE THERAPY, 2006, 13 (01) :29-39

[3] Protein transduction of dendritic cells for NY-ESO-1-based immunotherapy of myeloma [J].

Batchu, RB ;

Moreno, AM ;

Szmania, SM ;

Bennett, G ;

Spagnoli, GC ;

Ponnazhagan, S ;

Barlogie, B ;

Tricot, G ;

van Rhee, F .

CANCER RESEARCH, 2005, 65 (21) :10041-10049

[4] High-level expression of cancer/testis antigen NY-ESO-1 and human granulocyte-macrophage colony-stimulating factor in dendritic cells with a bicistronic retroviral vector [J].

Batchu, RB ;

Moreno, AM ;

Szmania, S ;

Gupta, SK ;

Zhan, F ;

Rosen, N ;

Kozlowski, M ;

Spencer, T ;

Spagnoli, GC ;

Shaughnessy, J ;

Barlogie, B ;

Tricot, G ;

van Rhee, F .

HUMAN GENE THERAPY, 2003, 14 (14) :1333-1345

[5] Design of an Optimized Wilms' Tumor 1 (WT1) mRNA Construct for Enhanced WT1 Expression and Improved Immunogenicity In Vitro and In Vivo [J].

Benteyn, Daphne ;

Anguille, Sebastien ;

Van Lint, Sandra ;

Heirman, Carlo ;

Van Nuffel, An M. T. ;

Corthals, Jurgen ;

Ochsenreither, Sebastian ;

Waelput, Wim ;

Van Beneden, Katrien ;

Breckpot, Karine ;

Van Tendeloo, Viggo ;

Thielemans, Kris ;

Bonehill, Aude .

MOLECULAR THERAPY-NUCLEIC ACIDS, 2013, 2 :e134

[6] Engineering Dendritic Cells to Enhance Cancer Immunotherapy [J].

Boudreau, Jeanette E. ;

Bonehill, Aude ;

Thielemans, Kris ;

Wan, Yonghong .

MOLECULAR THERAPY, 2011, 19 (05) :841-853

[7] Exploiting dendritic cells in the development of cancer vaccines [J].

Bracci, Laura ;

Capone, Imerio ;

Moschella, Federica ;

Proietti, Enrico ;

Belardelli, Filippo .

EXPERT REVIEW OF VACCINES, 2013, 12 (10) :1195-1210

[8] Immunological profiling of a panel of human ovarian cancer cell lines [J].

Carr, TiVany M. ;

Adair, Sara J. ;

Fink, Mitsu J. ;

Hogan, Kevin T. .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2008, 57 (01) :31-42

[9]

Chiriva-Internati M, 2002, EUR J IMMUNOL, V32, P30, DOI 10.1002/1521-4141(200201)32:1<30::AID-IMMU30>3.0.CO

[10]

2-E

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