| RRC ID |
57974
|
| Author |
Kanagawa N, Yanagawa T, Nakagawa T, Okada N, Nakagawa S.
|
| Title |
Tumor vessel-injuring ability improves antitumor effect of cytotoxic T lymphocytes in adoptive immunotherapy.
|
| Journal |
Cancer Gene Ther
|
| Abstract |
Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature.
|
| Volume |
20(1)
|
| Pages |
57-64
|
| Published |
2013-1-1
|
| DOI |
10.1038/cgt.2012.85
|
| PII |
cgt201285
|
| PMID |
23175243
|
| PMC |
PMC3534155
|
| MeSH |
Adoptive Transfer
Animals
Carcinoma, Lewis Lung / blood supply
Carcinoma, Lewis Lung / immunology
Carcinoma, Lewis Lung / therapy*
Cell Line, Tumor
Female
Humans
Immunotherapy, Adoptive*
Kidney / pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neoplasm Transplantation
Neovascularization, Pathologic / immunology
Neovascularization, Pathologic / therapy
Receptors, Antigen, T-Cell / biosynthesis
Recombinant Fusion Proteins / biosynthesis
Single-Chain Antibodies / biosynthesis
T-Lymphocytes, Cytotoxic / immunology*
T-Lymphocytes, Cytotoxic / metabolism
T-Lymphocytes, Cytotoxic / transplantation
Vascular Endothelial Growth Factor Receptor-2 / immunology
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Wound Healing / immunology
|
| Resource |
| Human and Animal Cells |
LLC(RCB0558) |
