Expansion and characterization of T cells transduced with a chimeric receptor against ovarian cancer

L. L. Parker, M. T. Do, J. A. Westwood, J. R. Wunderlich, M. E. Dudley, S. A. Rosenberg, P. Hwu

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Adoptive immunotherapy with genetically modified T lymphocytes is being utilized in clinical trials for the treatment of a broad range of diseases including cancer and HIV infection. To improve on these treatments, and to better understand their mechanisms of action, it is necessary to develop techniques to generate large numbers of cells and characterize the functional heterogeneity of the cells produced. In this study, patient peripheral blood lymphocytes were transduced with a chimeric antigen receptor (MOv-γ) derived from a mouse monoclonal antibody against folate-binding protein, which is overexpressed on many ovarian cancers. Thus, irrespective of their original specificity, normal human T lymphocytes were redirected to react against ovarian cancer cells. Lymphocytes from five patients were transduced and grown to large numbers, with a median expansion of more than 7000-fold. When proliferation was inadequate, the cells were expanded by stimulation utilizing anti-CD3, IL-2, and irradiated allogeneic PBMCs. The cells maintained their functional ability to recognize ovarian cancer over several months. Cloning of transduced cells was undertaken to determine the level of gene expression and function of individual cells making up the bulk population. Transduced CD4+ and CD8+ cell clones were isolated from the bulk and demonstrated antitumor activity. These clones had a diverse repertoire with respect to secretion of cytokines, and individual clones maintained their cytokine profile on subsequent expansion. These studies establish the feasibility of consistently generating large numbers of gene-modified tumor-reactive lymphocytes, with a stable and diverse cytokine repertoire, that could be utilized for patient treatment.

Original languageEnglish (US)
Pages (from-to)2377-2387
Number of pages11
JournalHuman gene therapy
Issue number17
StatePublished - Nov 20 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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