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Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.

Publication ,  Journal Article
Philip, R; Clary, B; Brunette, E; Kilinski, L; Murugesh, D; Sorich, M; Yau, J; Lebkowski, J; Lyerly, HK; Philip, M
Published in: Clin Cancer Res
January 1996

We have previously shown that cationic liposomes facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of breast and ovarian cancers, we have constructed an expression plasmid pMP6IL2 and investigated the use of liposome-mediated gene delivery into primary, uncultured human breast and ovarian tumor cells to produce interleukin 2 (IL-2)-secreting tumor cells. We have demonstrated significant levels of IL-2 expression in tumor cell lines and primary breast and ovarian tumor cells using this AAV-based expression plasmid complexed to cationic liposomes. Transfections with the non-AAV plasmid containing the identical expression cassette as the AAV plasmid induced IL-2 expression in the tumor cell line but failed to produce IL-2 in primary tumor cells. Significant levels of IL-2 were induced with the AAV plasmid regardless of liposome compositions used for transfection. The transfected breast cell line and primary tumor cells were able to express the transgene product for up to 28 days after lethal radiation. The transfection efficiency was comparable for both the tumor cell line and primary tumor cells and ranged from 20 to 50% for both cell types as assessed by intracellular IL-2 staining. Although the primary tumor cell preparations consist of mixed population of cells, at least 40% of the tumor cells expressed the transgene as assessed by immunostaining for IL-2. The ability to efficiently express transgenes in freshly isolated, nondividing tumor cells may potentiate active immunotherapy strategies for gene-based cancer treatment.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

January 1996

Volume

2

Issue

1

Start / End Page

59 / 68

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Plasmids
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Interleukin-2
  • Immunotherapy, Active
  • Humans
  • Genetic Therapy
  • Gene Transfer Techniques
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Philip, R., Clary, B., Brunette, E., Kilinski, L., Murugesh, D., Sorich, M., … Philip, M. (1996). Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer. Clin Cancer Res, 2(1), 59–68.
Philip, R., B. Clary, E. Brunette, L. Kilinski, D. Murugesh, M. Sorich, J. Yau, J. Lebkowski, H. K. Lyerly, and M. Philip. “Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.Clin Cancer Res 2, no. 1 (January 1996): 59–68.
Philip R, Clary B, Brunette E, Kilinski L, Murugesh D, Sorich M, et al. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer. Clin Cancer Res. 1996 Jan;2(1):59–68.
Philip, R., et al. “Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.Clin Cancer Res, vol. 2, no. 1, Jan. 1996, pp. 59–68.
Philip R, Clary B, Brunette E, Kilinski L, Murugesh D, Sorich M, Yau J, Lebkowski J, Lyerly HK, Philip M. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer. Clin Cancer Res. 1996 Jan;2(1):59–68.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

January 1996

Volume

2

Issue

1

Start / End Page

59 / 68

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Plasmids
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Interleukin-2
  • Immunotherapy, Active
  • Humans
  • Genetic Therapy
  • Gene Transfer Techniques
  • Female