Vaccination of women with metastatic breast cancer, using a costimulatory gene (CD80)-modified, HLA-A2-matched, allogeneic, breast cancer cell line: Clinical and immunological results

Annemieke Dols, John W. Smith, Sybren L. Meijer, Bernard A. Fox, Hong-Ming Hu, Edwin Walker, Sidney Rosenheim, Tarsem Moudgil, Teri Doran, William Wood, Mark Seligman, W. Gregory Alvord, Deric Schoof, Walter J. Urba

Research output: Contribution to journalArticleAcademicpeer-review


MDA-MB-231, an HLA-A2+, HER2/neu+ allogeneic breast cancer cell line genetically modified to express the costimulatory molecule CD80 (B7-1), was used to vaccinate 30 women with previously treated stage IV breast cancer. Expression of CD80 conferred the ability to deliver a costimulatory signal and thereby improved the antigen presentation capability of the tumor cells to patient T cells in vitro. Patients were vaccinated with 107 or 108 irradiated gene-modified tumor cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or BCG, three times at 2-week intervals and then monthly until progressive disease developed. GM-CSF-related flulike symptoms and minor injection site reactions were observed frequently. Prolonged disease stabilization was observed in four patients but no objective tumor regressions were seen. Immune responses were measured in matched peripheral blood samples collected before and after treatment from 9 of 15 patients treated at the 108 tumor cell dose. Four patients exhibited MHC class I-restricted cytokine production in response to the parental breast cancer cell line. One patient maintained an increased number of circulating tumor-specific, interferon γ-secreting CD8+ T cells for 24 months after the last vaccination. One patient exhibited a tumor-specific interleukin 5 response to an autologous tumor cell line. This immunization strategy proved to be safe and feasible, and induced tumor-specific immune responses in a minority of patients; however, no objective tumor regressions were observed.

Original languageEnglish
Pages (from-to)1117-1123
Number of pages7
JournalHuman Gene Therapy
Issue number11
Publication statusPublished - 20 Jul 2003
Externally publishedYes

Cite this