The “Bystander Effect”: Tumor Regression When a Fraction of the Tumor Mass Is Genetically Modified

Scott M. Freeman, Camille N. Abboud, Katharine A. Whartenby, Charles H. Packman, David S. Koeplin, Frederick L. Moolten, George N. Abraham

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor cells expressing the herpes simplex virus thymidine kinase (HSV-TK) gene are sensitive to the drug ganciclovir (GCV). We demonstrate here that HSV-TK-positive cells exposed to GCV were lethal to HSV-TK-negative cells as a result of a “bystander effect” HSV-TK-negative cells were killed in vitro when the population of cultured cells contained only 10% HSV-TK-positive cells. The mechanism of this “bystander effect” on HSV-TK-negative cells appeared to be related to the process of apoptotic cell death when HSV-TK-positive cells were exposed to GCV. Flow cytometric and electron microscopic analyses suggested that apoptotic vesicles generated from the dying gene-modified cells were phagocytized by nearby, unmodified tumor cells. Prevention of apoptotic vesicle transfer prevented the bystander effect.

Original languageEnglish (US)
Pages (from-to)5274-5283
Number of pages10
JournalCancer Research
Volume53
Issue number21
StatePublished - Nov 1993
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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