       Document 0968
 DOCN  M9460968
 TI    Human tumor cells secreting IL-2 induce a locally protective immune
       response against tumor engraftment (Meeting abstract).
 DT    9406
 AU    Alosco TR; Gansbacher B; Bankert RB; Takita H; Petrelli NJ; Roswell Park
       Cancer Inst., Buffalo, NY
 SO    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
 AB    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.
 DE    Adenosine Deaminase/GENETICS  Animal  Human
       Interleukin-2/GENETICS/*SECRETION  Lung Neoplasms/*SECRETION  Mice
       Mice, SCID  Retroviridae/GENETICS  Transfection  Tumor Cells, Cultured
       MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

