Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Human tumor cells secreting IL-2 induce a locally protective immune response against tumor engraftment (Meeting abstract).
Society of Surgical Oncology, 46th Annual Cancer Symposium in Conjunction with Society of Head and Neck Surgeons. March 18-21, 1993, Los Angeles, CA, p. 107, 1993.. Unique Identifier : AIDSLINE ICDB/94697346 Alosco TR; Gansbacher B; Bankert RB; Takita H; Petrelli NJ; Roswell Park Cancer Inst., Buffalo, NY
Abstract:
The retroviral transfection of cytokine genes into tumor cells and the subsequent secretion of various cytokines has lead to regression of weakly immunogenic murine tumors. The purpose of our study was to demonstrate that a similar transfection of the IL-2 (interleukin-2) gene into human tumor cell lines can be done and that the tumor cells will subsequently secrete IL-2 and become more immunogenic. A retroviral vector containing the bacterial neomycin resistance gene derived from the genome of Maloney murine leukemia virus was fused to human IL-2 or ADA (adenosine deaminase) cDNA. Retroviral vector constructs were converted to corresponding virus using established procedures. Human lung tumor cell lines were generated from operative specimens and exposed to the retroviral vectors. Colonies secreting 0.5-25 Cetus U/ml of IL-2 were isolated by G418 (neomycin) selection and expanded to cell lines. Cell lines transfected with the ADA gene instead of the IL-2 gene were used as controls. Using the C.B17 SCID (severe combined immunodeficiency) mouse, we have observed that the local secretion of IL-2 by a murine tumor initiates effector cells of the NK cell and monocyte, macrophage lineage that can, in the absence of functional T cells, eliminate the tumor. The secretion of IL-2 has a locally protective effect on the tumorigenicity of the parental cell line, but did not have any protective effect when placed at a distant site in the SCID mouse thereby underscoring the importance of the sustained local release of IL-2. We similarly show that transfection of the IL-2 gene into a human squamous cell carcinoma of the lung, as well as a large cell lung tumor, will abrogate tumorigenicity for up to 3 months observed, whereas the parental cell line, cell lines secreting low (less than 10 U/ml) levels of IL-2, and the cell lines transfected with the ADA gene grow aggressively in the SCID mouse by 4-6 weeks. The local secretion of IL-2 by the transfected cell line also inhibited tumor formation by the parental cell line. These results indicate that (1) transfection of the IL-2 gene into human tumors can be done; (2) subsequent secretion of IL-2 will occur; and (3) the local secretion of IL-2 by tumor cells will induce an antitumor response by the host.
Keywords: Adenosine Deaminase/GENETICS Animal Human Interleukin-2/GENETICS/*SECRETION Lung Neoplasms/*SECRETION Mice Mice, SCID Retroviridae/GENETICS Transfection Tumor Cells, Cultured ABSTRACT 940630
M9460924
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
