Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen

Pauline W. Chen, Michael Wang, Vincenzo Bronte, Yifan Zhai, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticlepeer-review

Abstract

Recombinant adenovirus (rAd), deleted of critical genes that enable viral replication and replaced with genes encoding heterologous proteins, has been shown to be a safe and effective vector in gene therapy studies. To evaluate a potential role for rAd as an immunogen, we used two different replication- defective type 2 rAds encoding the model Ag, β-galactosidase (β-gal). To determine whether rAd elicited the kind of immune responses therapeutic in an anti-tumor setting, the β-gal-expressing adenocarcinoma, CT26.CL25, was used. Splenocytes from BALB/c mice immunized with 1 x 107 infectious units (iu) of rAd demonstrated anti-β-gal activity after in vitro culture with the relevant L(d) β-gal peptide. Adoptive transfer of these same splenocytes produced dramatic regression of established pulmonary metastases. However, when tumor-bearing mice were treated with 1 x 107 iu of rAd, no reduction in established disease was observed even when rAd was given with exogenous IL- 2. To increase the viral dose delivered to each animal, we used an E1/E4- deleted rAd that could be grown to much higher titers. Significant reduction occurred when 10-fold more rAd (1 x 108 iu) was administered. Exogenous IL- 2 administration with 1 x 108 iu of rAd resulted in augmentation of this anti-tumor effect. These findings demonstrate that when using a nonreplicating virus, the viral dose is directly related to the immune response generated. These data constitute the first reported use of rAd in the treatment of an established experimental cancer and may have implications for the treatment of human cancer.

Original languageEnglish (US)
Pages (from-to)224-231
Number of pages8
JournalJournal of Immunology
Volume156
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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