Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: Implications for gene therapy

Tal Kafri, David Morgan, Troy Krahl, Nora Sarvetnick, Linda Sherman, Inder Verma

Research output: Contribution to journalArticlepeer-review

217 Scopus citations

Abstract

Replication-defective adenoviral (RDAd) vectors can be generated at high titers and infect both dividing and nondividing cells. Long term expression in the transduced tissue, however, has been a problem because of the cellular immune responses against the infected cells. We demonstrate that mice injected with RDAd vectors containing mouse leptin gene reduce food intake and lose weight for only 7 to 10 days. Splenocytes obtained from infected mice are able to lyse target cells infected with RDAd vectors. Surprisingly, target cells infected with psoralen-treated, UV-crosslinked, biologically inactive RDAd also were lysed efficiently by the effector cells. Furthermore, splenocytes obtained from mice injected with inactive RDAd vectors efficiently lysed target cells infected with RDAd vectors. Whether RDAd vectors were injected i.m. or i.v. or through an i.p. route, the extent of lysis was similar. We propose that cells infected with RDAd vectors present antigens for recognition by class 1 major histocompatibility complex- restricted cytotoxic T lymphocytes by a mechanism that does not require viral replication or de novo protein synthesis. These results should prompt reevaluation of the use of RDAd vectors for gene therapy when long-term expression is required.

Original languageEnglish (US)
Pages (from-to)11377-11382
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number19
DOIs
StatePublished - Sep 15 1998

ASJC Scopus subject areas

  • General

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