Journal
CANCER GENE THERAPY
Volume 20, Issue 10, Pages 564-575Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2013.53
Keywords
cancer vaccines; EAT-2; immune modulation; innate immunity; SLAM receptors; SAP adaptors; carcinoembryonic antigen
Categories
Funding
- NIH [RO1DK-069884, P01CA078673]
- Michigan State University (MSU) Foundation
- Osteopathic Heritage Foundation
- King Abdullah bin Abdulaziz Scholarship grant, Ministry of Higher Education, Kingdom of Saudi Arabia
- NIH National Institute of Dental and Craniofacial Research [DE13513, 1F31DE022696-01]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available