Simultaneous transduction of B7-1 and IL-2 genes into human melanoma cells to be used as vaccine: enhancement of stimulatory activity for autologous and allogeneic lymphocytes |
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Authors: | Arabella Mazzocchi Cecilia Melani Licia Rivoltini Chiara Castelli Michele Del Vecchio Claudia Lombardo Mario P Colombo Giorgio Parmiani |
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Institution: | (1) Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy e-mail: parmiani@istitutotumori.mi.it Fax: +39-02-2390630, IT;(2) Unit of Gene Therapy – Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy, IT;(3) Unit of Immunohematology – Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy, IT |
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Abstract: | In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for
expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase,
with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector. The lines were selected to
share only the HLA-A*0201 allele to avoid generation of strong alloreactivity in case of their multiple in vivo use in HLA-A*0201
+ patients. Phenotypic and functional analysis of B7-1-IL2 transduced melanoma lines in comparison with B7-1 transduced and/or
parental untransduced counterparts were then carried out. Tumor cells expressing either B7-1 or both genes did not change
their original antigenic profile. From a functional point of view, expression of both genes in melanoma lines: (1) improved
the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold
levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate
cytotoxicity and interferon-γ release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation
of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients. Thus, B7-IL2 gene-transduced
melanoma lines appear to display a high immunogenicity and could be used as vaccine in melanoma patients.
Received: 17 August 2000 / Accepted: 1 February 2001 |
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Keywords: | B7-1 IL-2 Melanoma Vaccine |
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