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Immunological memory induced by genetically transduced tumor cells

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Abstract

Background: Recent studies have demonstrated the usefulness of gene-modified tumor cells for immunotherapy. Using the tumorigenic murine fibrosarcoma, MCA 106, we investigated the effects of localized interferon-γ (IFNg) secretion on tumorigenicity and on long-term memory.

Methods: The murine IFNg (MuIFNg) gene was introduced into tumor cells. High and low IFNg-secreting clones were isolated. C57BL/6 mice were injected subcutaneously (s.c.) with either parental (P), high or low IFNg-secreting (H- or L-IFNg) cells, and tumor growth was assessed weekly. Spleens were harvested on different days postinjection (p.i.) to assess in vitro cytolytic activity. In parallel, tissues from injection sites were stained with macrophage-, CD4-, and CD8-detecting antibodies. Mice were injected s.c. with H-IFNg MCA106 tumor. After 150 days the animals were rechallenged s.c. with MCA106P in one leg and with irrelevant syngeneic tumor in the other.

Results: Both P- and L-IFNg cells had similar growth, whereas the H-IFNg cells never grew. Only splenocytes from the H-IFNg animals showed in vitro CTL activity persisting until day 30 p.i. Histological data revealed a macrophage and CD4+ infiltrate much earlier in the H-IFNg group compared with the P group. Only the irrelevant, syngeneic tumor grew in animals previously injected with H-IFNg cells, whereas both P and irrelevant syngeneic tumors grew in controls.

Conclusions: Transduction of MCA106 cells with the MuIFNg gene diminished in vivo tumorigenicity in proportion to the amount of IFNg secreted. Immunization with H-IFNg cells elicited a host response characterized by macrophages and CD4+ cells. Long-term tumor-specific memory was seen after immunization with H-IFNg cells.

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Authors and Affiliations

  1. Viagene Inc., San Diego, California, USA

    Jack Barber PhD

  2. Department of Surgery, Duke University Medical Center, Box 3966, 27710, Durham, NC, USA

    Mohammed M. Dar AB, Zeinab Abdel-Wahab PhD, Carol E. Vervaert MT, Tim Darrow PhD &  H. F. Seigler MD

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  2. Zeinab Abdel-Wahab PhD
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Dar, M.M., Abdel-Wahab, Z., Vervaert, C.E. et al. Immunological memory induced by genetically transduced tumor cells. Annals of Surgical Oncology 3, 247–254 (1996). https://doi.org/10.1007/BF02306279

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