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PMID: 7730632 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

IL-2 enhances the function of recombinant poxvirus-based vaccines in the treatment of established pulmonary metastases.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 154 ·No. 10 ·1995-05-15 ·Pages 5282-92

Bronte V, Tsung K, Rao JB, Chen PW, Wang M, Rosenberg SA, Restifo NP

Abstract

Neoplastic cells are generally poor immunogens. Transfection of the murine tumor CT-26 with beta-galactosidase (beta-gal), a protein from Escherichia coli, did not alter its growth rate in vivo, or its lethality, and did not elicit a measurable anti-beta-gal immune response. Immunization with beta-gal-expressing recombinant vaccinia viruses (rVV) elicited specific anti-beta-gal cytolytic T lymphocytes, but rVV-beta-gal was only marginally therapeutic when given to tumor-bearing mice. With the aim of expanding the immune response against beta-gal, used here as a model tumor Ag, we gave mice exogenous IL-2 starting 12 h after the poxvirus. The therapeutic effectiveness of the combination of poxvirus and IL-2 was far greater than either of these treatments alone. When the cDNA for IL-2 was inserted into the viral genome of the rVV construct to make a double recombinant (drVV), antitumor activity was further augmented. One mechanism of action may be the enhanced activation or expansion of cytotoxic T cells, because a marked increase in primary cytotoxic responses against vaccinia determinants was observed. Interestingly, other cytokines (mGM-CSF, mTNF-alpha, and mIFN-gamma) inserted into the rVV genome did not modify the efficacy of the rVV constructs. The increase in specific CTL responses against beta-gal by drVV expressing the tumor-associated Ags (TAA) and IL-2 was more pronounced in mice bearing the lacZ-transduced tumor than in those bearing the parental cell line, suggesting that the TAA presented by growing tumor cells can either pre-activate or otherwise amplify the immune response induced by the rVV. Unfortunately, in several long-term surviving mice, tumor recurred that no longer expressed beta-gal. These results indicate that treatment of disseminated tumors by using recombinant viruses expressing TAA can be enhanced by IL-2 provided exogenously, or encoded within the recombinant virus.

MeSH Terms
Amino Acid Sequence Animals Antigens, Neoplasm/immunology Interleukin-2/biosynthesis,therapeutic use Lung Neoplasms/immunology,secondary,therapy Mice Mice, Inbred BALB C Molecular Sequence Data Poxviridae/immunology Recombinant Proteins/biosynthesis,therapeutic use T-Lymphocytes, Cytotoxic/immunology Vaccines, Synthetic/therapeutic use Vaccinia virus/immunology beta-Galactosidase/immunology
Chemicals
Antigens, Neoplasm Interleukin-2 Recombinant Proteins Vaccines, Synthetic beta-Galactosidase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bronte V
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tsung K
Rao J B
Chen P W
Wang M
Rosenberg S A
Restifo N P
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
0022-1767
Published
1995-05-15
Pages
5282-92
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2041892
Subset
IM
Grants
Intramural NIH HHS · Z01 BC010763-01 · United States
Intramural NIH HHS · Z99 CA999999 · United States
External Links
PubMed source PMC Full Text View journal details
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