Abstract |
The signaling lymphocytic activation molecule-associated adaptor Ewing's sarcoma's-activated transcript 2 (EAT-2) is primarily expressed in dendritic cells, macrophages and natural killer cells. Including EAT-2 in a vaccination regimen enhanced innate and adaptive immune responses toward pathogen-derived antigens, even in the face of pre-existing vaccine immunity. Herein, we investigate whether co-vaccinations with two recombinant Ad5 (rAd5) vectors, one expressing the carcinoembryonic antigen (CEA) and one expressing EAT-2, can induce more potent CEA-specific cytotoxic T lymphocyte (CTL) and antitumor activity in the therapeutic CEA-expressing MC-38 tumor model. Our results suggest that inclusion of EAT-2 significantly alters the kinetics of Th1-biasing proinflammatory cytokine and chemokine responses, and enhances anti-CEA-specific CTL responses. As a result, rAd5-EAT2-augmented rAd5-CEA vaccinations are more efficient in eliminating CEA-expressing target cells as measured by an in vivo CTL assay. Administration of rAd5-EAT2 vaccines also reduced the rate of growth of MC-38 tumor growth in vivo. Also, an increase in MC-38 tumor cell apoptosis (as measured by hematoxylin and eosin staining, active caspase-3 and granzyme B levels within the tumors) was observed. These data provide evidence that more efficient, CEA-specific effector T cells are generated by rAd5 vaccines expressing CEA, when augmented by rAd5 vaccines expressing EAT-2, and this regimen may be a promising approach for cancer immunotherapy in general.
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Authors | Y A Aldhamen, S S Seregin, Y A Kousa, D P W Rastall, D M Appledorn, S Godbehere, B C Schutte, A Amalfitano |
Journal | Cancer gene therapy
(Cancer Gene Ther)
Vol. 20
Issue 10
Pg. 564-75
(Oct 2013)
ISSN: 1476-5500 [Electronic] England |
PMID | 23949283
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Antigens, CD
- Cancer Vaccines
- Carcinoembryonic Antigen
- Receptors, Cell Surface
- Sh2d1b1 protein, mouse
- Signaling Lymphocytic Activation Molecule Family Member 1
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Topics |
- Adaptor Proteins, Signal Transducing
(biosynthesis, genetics, immunology)
- Adenoviridae
(genetics)
- Animals
- Antigens, CD
(genetics, immunology)
- Cancer Vaccines
(genetics, immunology, pharmacology)
- Carcinoembryonic Antigen
(biosynthesis, genetics, immunology)
- Genetic Vectors
(genetics)
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Random Allocation
- Receptors, Cell Surface
(genetics, immunology)
- Signaling Lymphocytic Activation Molecule Family Member 1
- T-Lymphocytes, Cytotoxic
(drug effects, immunology)
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