Abstract:
: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 IFN-γ, 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.
journal_name
Vaccinejournal_title
Vaccineauthors
Batchu RB,Gruzdyn OV,Moreno-Bost AM,Szmania S,Jayandharan G,Srivastava A,Kolli BK,Weaver DW,van Rhee F,Gruber SAdoi
10.1016/j.vaccine.2013.12.049subject
Has Abstractpub_date
2014-02-12 00:00:00pages
938-43issue
8eissn
0264-410Xissn
1873-2518pii
S0264-410X(13)01792-1journal_volume
32pub_type
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