Cytotoxic T lymphocyte responses to proteins encoded by heterologous transgenes transferred in vivo by adenoviral vectors

Wenru Song, Hwai Loong Kong, Paula Traktman, Ronald Crystal

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Although replication-deficient adenovirus (Ad) vectors are efficient vehicles for in vivo gene transfer, persistence of expression of the Ad genome is limited in immunocompetent hosts by cellular immunity directed against the gene product of the vector. While most attention has been focused on cytotoxic T lymphocytes (CTL) directed against the low-level early and late Ad gene expression in the Ad vector-infected target cells, significant cellular immunity is likely also directed against the product of heterologous transgenes. To evaluate this concept, in vivo generation of CTL was evaluated in C57B1/6 and BALB/c mice with Ad vectors expressing a variety of heterologous transgenes, including Escherichia coli chloramphenicol acetyl transferase (CAT), β-galactosidase (β-Gal), cytosine deaminase, and human thrombopoietin (hTPO), with an Ad vector expressing no transgene ('null') as a control. Following intravenous administration of Ad vectors, spleen cells were harvested 2 weeks later, stimulated for 5 days with syngeneic cells infected with various Ad vectors, and then evaluated for CTL activity using 51Cr-release from syngeneic Ad vector-infected targets. In all cases, CTL directed against the heterologous transgene products was observed, although there were differences in the amounts of transgene-specific CTL. CTL directed against the transgene were also observed with other routes of administration, including intratracheal, subcutaneous, and intraperitoneal administration. These observations suggest that inclusion of a heterologous transgene in Ad vectors enhances the elimination of vector-infected cells, a circumstance that will be partially circumvented using autologous genes. For some applications, specific immune responses to products of transgenes delivered by Ad vectors might be exploited for therapeutic purposes.

Original languageEnglish
Pages (from-to)1207-1217
Number of pages11
JournalHuman Gene Therapy
Volume8
Issue number10
Publication statusPublished - 1 Jul 1997
Externally publishedYes

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Cytotoxic T-Lymphocytes
Transgenes
Adenoviridae
Proteins
Cellular Immunity
Cytosine Deaminase
Galactosidases
Genes
Thrombopoietin
Chloramphenicol
Transferases
Intravenous Administration
Spleen
Genome
Escherichia coli
Gene Expression

ASJC Scopus subject areas

  • Genetics

Cite this

Cytotoxic T lymphocyte responses to proteins encoded by heterologous transgenes transferred in vivo by adenoviral vectors. / Song, Wenru; Kong, Hwai Loong; Traktman, Paula; Crystal, Ronald.

In: Human Gene Therapy, Vol. 8, No. 10, 01.07.1997, p. 1207-1217.

Research output: Contribution to journalArticle

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