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Gene transfer of AIMP1 and B7.1 into epitope-loaded, fibroblasts induces tumor-specific CTL immunity, and prolongs the survival period of tumor-bearing mice

Authors
Kim, Tae S.Lee, Byeong C.Kim, EugeneCho, DaehoCohen, Edward P.
Issue Date
5-Nov-2008
Publisher
ELSEVIER SCI LTD
Keywords
Fibroblast; AIMP1; B7.1; Tumor immunity; Vaccine
Citation
VACCINE, v.26, no.47, pp 5928 - 5934
Pages
7
Journal Title
VACCINE
Volume
26
Number
47
Start Page
5928
End Page
5934
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14150
DOI
10.1016/j.vaccine.2008.08.051
ISSN
0264-410X
1358-8745
Abstract
T helper type I (Th1) cell-mediated immune responses play Various roles in cellular immunity, including inducing cytotoxic T lymphocytes (CTLs) and they have been shown to be crucial in cancer immunotherapy. Previously, we found that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) stimulated antigen-presenting cells to secrete IL-12, leading to enhanced Th I cell responses. In this Study, as a way of enhancing antigen-specific Th1 responses, mouse fibroblasts (H-2(b)) were genetically modified to express an AIMP I and a costimulatory B7.1 (Fb/AIMP1/B7.1). Fb/AIMP1/B7.1 cells were then loaded with an ovalbumin epitope as a model antigen (Fb/AIMP1/B7.1/OVA), and tested to determine if they induced OVA-specific cas in C57BL/6 mice (H-2(b)). Immunization with Fb/AIMP1/B7.1/OVA cells induced strong cytotoxic activities against OVA-expressing EG7 tumor cells, but not against other H-2(b) tumor cells. The levels of the cytotoxic response in the immunized mice with Fb/AIMP1/137.1/OVA cells were significantly higher than the responses in mice immunized with other cell constructs. CD8(+) T cells were a major cell-type of OVA-specific antitumor immunity induced by Fb/AIMP1/B7.1/OVA cells. Furthermore, treatment with Fb/AIMP1/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor-bearing mice. These results indicate that AIMP1-secreting, epitope-loaded fibroblasts efficiently induce antigen-specific CTL responses in mice. (C) 2008 Elsevier Ltd. All rights reserved.
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