Transfection of interleukin 2 gene into human melanoma cells augments cellular immune response.

A preclinical model was used to determine if transfection of the interleukin 2 (IL-2) gene into human melanoma cells would augment the response of autologous and allogeneic peripheral blood lymphocytes (PBLs) from melanoma patients. IL-2 gene was transfected into three human melanoma cell lines; secretion of IL-2 from stable transfected cells was confirmed by enzyme-linked immunosorbent assay. The PBL response to these melanoma cells was then examined in a mixed-lymphocyte tumor reaction using PBLs from eight melanoma patients. The PBL response to autologous (P < 0.01) or human leukocyte antigen A cross-reactive (P < 0.05) transfected melanoma cells was significantly higher than it was to nontransfected melanoma cells. These data suggest that IL-2 gene transfection may be an important strategic approach to enhancing specific immune responses induced by a polyvalent melanoma cell vaccine.

[1]  D. Morton,et al.  Interleukin 4 receptor expression and growth inhibition of gastric carcinoma cells by interleukin 4. , 1992, Cancer research.

[2]  R. Elashoff,et al.  Prolongation of Survival in Metastatic Melanoma After Active Specific Immunotherapy With a New Polyvalent Melanoma Vaccine , 1992, Annals of surgery.

[3]  D. Morton,et al.  Induction of CD4+ cytotoxic T cells by sensitization with allogeneic melanomas bearing shared or cross-reactive HLA-A. , 1992, Cellular immunology.

[4]  S. Rosenberg,et al.  Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. , 1992, Journal of immunology.

[5]  H. Seigler,et al.  MHC-restricted recognition of autologous melanoma by tumor-specific cytotoxic T cells. Evidence for restriction by a dominant HLA-A allele. , 1991, Journal of immunology.

[6]  P. Kourilsky,et al.  Interleukin 2‐dependent activation of tumor‐specific cytotoxic T lymphocytes in vivo , 1991, European journal of immunology.

[7]  S. Eccles,et al.  Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL‐2 cDNA , 1991, International journal of cancer.

[8]  E. Gilboa,et al.  Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity , 1990, The Journal of experimental medicine.

[9]  D. Morton,et al.  Suppressor cell activity in a randomized trial of patients receiving active specific immunotherapy with melanoma cell vaccine and low dosages of cyclophosphamide. , 1990, Cancer research.

[10]  B. Vogelstein,et al.  Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response , 1990, Cell.

[11]  M. V. Doyle,et al.  Quantitation of mRNA by the polymerase chain reaction. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. Morton,et al.  An epitope common to gangliosides O-acetyl-GD3 and GD3 recognized by antibodies in melanoma patients after active specific immunotherapy. , 1989, Cancer research.

[13]  B. Cullen.  Expression of a cloned human interleukin-2 cDNA is enhanced by the substitution of a heterologous mRNA leader region. , 1988, DNA.

[14]  P. Terasaki,et al.  Significance of the HLA molecular structure to transplantation. , 1988, Clinical transplants.

[15]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[16]  R. Coffman,et al.  Two Types of Mouse Helper T Cell Clone: Differences in B Cell Help and Lymphokine Synthesis , 1987 .

[17]  J. Lowenthal,et al.  Interleukin 2 is both necessary and sufficient for the growth and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. , 1985, Journal of immunology.