Abstract
IL-2-dependent activated cells undergo apoptotic death when IL-2 is withdrawn either in vitro or after in vivo cell transfer. To attempt to sustain their survival after IL-2 withdrawal, melanoma-reactive human T lymphocytes were retrovirally transduced with an exogenous human IL-2 gene. Transduced PBMC and cloned CD8+ T cells produced IL-2 and maintained viability after IL-2 withdrawal. Upon restimulation, IL-2 transductants proliferated in the absence of exogenous IL-2 and could be actively grown, and their survival could be maintained without added IL-2 for over 8 wk. PBMCs similarly transduced with a control vector did not produce IL-2 and failed to proliferate in the absence of IL-2. A CD8+ T cell clone, when transduced with an IL-2 gene, manifested the same phenotypes as PBMCs in the absence of exogenous IL-2. Furthermore, an Ab reactive with the alpha-chain of IL-2R complex reduced the viability mediated by IL-2 secretion of the IL-2 transductants. Moreover, transduction of an IL-2 gene did not affect the high degree of recognition and specificity of transductants against melanoma targets. These tumor-reactive IL-2 transductants may be valuable for in vitro studies and for improved adoptive transfer therapies for patients with metastatic melanoma.
MeSH terms
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Autocrine Communication / genetics
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Autocrine Communication / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology
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Cancer Vaccines / immunology
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Cancer Vaccines / pharmacology
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Cell Division / genetics
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Cell Division / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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Clone Cells / immunology
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Clone Cells / metabolism
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Clone Cells / pathology
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Coculture Techniques
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Culture Media, Conditioned / metabolism
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Culture Media, Conditioned / pharmacology
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Humans
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Immunotherapy, Adoptive* / methods
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Interleukin-2 / genetics*
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Interleukin-2 / metabolism
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Interleukin-2 / pharmacology*
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Lymphocyte Activation / genetics
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Melanoma / genetics*
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Melanoma / immunology*
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Melanoma / pathology
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Melanoma / therapy
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / pharmacology
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Peptide Fragments / immunology
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Peptide Fragments / pharmacology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / pathology*
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Transduction, Genetic* / methods
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Tumor Cells, Cultured
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gp100 Melanoma Antigen
Substances
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Cancer Vaccines
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Culture Media, Conditioned
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Interleukin-2
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Membrane Glycoproteins
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PMEL protein, human
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Peptide Fragments
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gp100 Melanoma Antigen