| Autor: |
Bobisse S; Department of Oncology, University of Padova, Padova, Italy., Rondina M, Merlo A, Tisato V, Mandruzzato S, Amendola M, Naldini L, Willemsen RA, Debets R, Zanovello P, Rosato A |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer research [Cancer Res] 2009 Dec 15; Vol. 69 (24), pp. 9385-94. |
| DOI: |
10.1158/0008-5472.CAN-09-0494 |
| Abstrakt: |
T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers of tumor-specific T cells. TCR alpha and beta chains were isolated from a highly lytic HLA-A2-restricted cytotoxic T lymphocyte (CTL) clone recognizing the melanoma-associated Melan-A/MART-1 antigen and inserted into a lentiviral vector carrying a bidirectional promoter capable of robust and coordinated expression of the two transgenes. Lentiviral vector-based gene delivery systems have shown increased transfer efficiency and transgene expression compared with the widely used gamma-retroviral vectors. This vector performed more efficiently than a gamma-retrovirus-based vector containing the same expression cassette, resulting in a T-cell population with 60% to 80% of transgenic TCR expression with mainly CD8(+) intermediate effector phenotype. Transgenic T cells specifically produced cytokine in response to and killed antigen-expressing melanoma cells, retained an overlapping functional avidity in comparison with the TCR donor CTL clone, and exerted significant therapeutic effects in vivo upon adoptive transfer in melanoma-bearing severe combined immunodeficient mice. Optical imaging showed their accumulation in the tumor site. Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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