Interleukin-Gene-Transduced Human Melanoma Cells Efficiently Stimulate MHC-Unrestricted and MHC-Restricted Autologous Lymphocytes

Flavio Arienti, Josep Sulé-Suso, Cecilia Melani, Cristina Maccalli, Filiberto Belli, Maria Teresa Illeni, Andrea Anichini, Natale Cascinelli, Mario Paolo Colombo, Giorgio Parmiani

Research output: Contribution to journalArticle

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Abstract

Two human melanoma lines were transduced by a retroviral vector with the gene of the human interleukin-2 (IL-2) and characterized for their immunological properties in comparison with the parental lines. Transduction resulted in the production of biologically active IL-2 in the average amounts of 2,282 and 2,336 pg/ml per 105 cells per 24 hr over 3 and 2 months by the Mel4932/IL-2 and the MelB6/IL-2 lines, respectively. Melanoma-transduced cells lost their tumorigenicity in nude mice. No major changes in the phenotype were observed in IL-2 gene-transduced lines. In fact, more than 90% of cells expressed class I and II(DR) HLA, adhesion molecules, integrins, and melanoma-associated antigens. Irradiation with 100–400 Gy, while inhibiting tumor cell growth in vitro, allowed the release of IL-2 by the transduced cells for at least 5 weeks. The two melanoma lines also maintained susceptibility to lysis by lymphokine-activated killer (LAK) cells and by a HLA-A2-restricted melanoma-specific cytotoxic T lymphocyte (CTL) clone recognizing the melanoma antigen (Melan-A). In a limiting dilution assay, transduced, but not parental melanoma lines unless added with an amount of IL-2 comparable to that released by the transduced cells, were able to expand both nonspecific and melanoma-specific CTL precursors from autologous peripheral blood lymphocytes (PBL). In mixed lymphocytes-tumor cultures, IL-2 gene-transduced melanoma cells stimulated the expansion of major histocompatibility complex (MHC)-unrestricted effectors from autologous PBL, and of CD3+ CD8+ MHC-restricted CTL from tumor-invaded lymph nodes. These results indicate that IL-2 gene transduction does not alter significantly the expression of the immunologically relevant molecules of human melanoma lines while increasing their ability to stimulate both specific and nonspecific lymphocyte responses. These lines will be of value in the vaccination of melanoma patients.

Original languageEnglish
Pages (from-to)1139-1150
Number of pages12
JournalHuman Gene Therapy
Volume5
Issue number9
DOIs
Publication statusPublished - 1 Sep 1994
Externally publishedYes

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Interleukins
Major Histocompatibility Complex
Interleukin-2
Melanoma
Lymphocytes
Genes
Cytotoxic T-Lymphocytes
Melanoma-Specific Antigens
HLA-A2 Antigen
Lymphokine-Activated Killer Cells
Neoplasms
Nude Mice
Integrins
Vaccination
Clone Cells
Lymph Nodes
Phenotype
Growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Interleukin-Gene-Transduced Human Melanoma Cells Efficiently Stimulate MHC-Unrestricted and MHC-Restricted Autologous Lymphocytes. / Arienti, Flavio; Sulé-Suso, Josep; Melani, Cecilia; Maccalli, Cristina; Belli, Filiberto; Illeni, Maria Teresa; Anichini, Andrea; Cascinelli, Natale; Colombo, Mario Paolo; Parmiani, Giorgio.

In: Human Gene Therapy, Vol. 5, No. 9, 01.09.1994, p. 1139-1150.

Research output: Contribution to journalArticle

Arienti, F, Sulé-Suso, J, Melani, C, Maccalli, C, Belli, F, Illeni, MT, Anichini, A, Cascinelli, N, Colombo, MP & Parmiani, G 1994, 'Interleukin-Gene-Transduced Human Melanoma Cells Efficiently Stimulate MHC-Unrestricted and MHC-Restricted Autologous Lymphocytes', Human Gene Therapy, vol. 5, no. 9, pp. 1139-1150. https://doi.org/10.1089/hum.1994.5.9-1139
Arienti, Flavio ; Sulé-Suso, Josep ; Melani, Cecilia ; Maccalli, Cristina ; Belli, Filiberto ; Illeni, Maria Teresa ; Anichini, Andrea ; Cascinelli, Natale ; Colombo, Mario Paolo ; Parmiani, Giorgio. / Interleukin-Gene-Transduced Human Melanoma Cells Efficiently Stimulate MHC-Unrestricted and MHC-Restricted Autologous Lymphocytes. In: Human Gene Therapy. 1994 ; Vol. 5, No. 9. pp. 1139-1150.
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AU - Sulé-Suso, Josep

AU - Melani, Cecilia

AU - Maccalli, Cristina

AU - Belli, Filiberto

AU - Illeni, Maria Teresa

AU - Anichini, Andrea

AU - Cascinelli, Natale

AU - Colombo, Mario Paolo

AU - Parmiani, Giorgio

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