Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication.

Abstract

In two murine lung cancer models adenoviral interleukin 7-transduced dendritic cells (DC-AdIL-7) were administered intratumorally, resulting in complete tumor regression. Intratumoral DC-AdIL-7 therapy was as effective as DCs pulsed with specific tumor peptide antigens. Comparison with other intratumoral therapies including recombinant IL-7, AdIL-7 vector alone, unmodified DCs, IL-7-transduced fibroblasts, or DCs pulsed with tumor lysates revealed DC-AdIL-7 therapy to be superior in achieving antitumor responses and augmenting immunogenicity. Mice with complete tumor eradication as a result of either DC-AdIL-7 or AdIL-7 therapy were rechallenged with parental tumor cells 30 days or more after complete tumor eradication. All the DC-AdIL-7-treated mice completely rejected a secondary rechallenge, whereas the AdIL-7-treated mice had sustained antitumor effects in only 20-25% of the mice. DC-AdIL-7 therapy was more effective than AdIL-7 in achieving systemic antitumor responses and enhancing immunogenicity. After complete tumor eradication, those mice treated with DC-AdIL-7 evidenced significantly greater release of splenocyte GM-CSF and IFN-gamma than did controls or AdIL-7-treated mice. After intratumoral injection, gene-modified DCs trafficked from the tumor to lymph node sites and spleen. DCs were detected in nodal tissues for up to 7 days after intratumoral injection. We report that intratumoral DC-AdIL-7 leads to significant systemic immune responses and potent antitumor effects in murine lung cancer models.

• Authors: P W Miller, S Sharma, M Stolina, L H Butterfield, J Luo, Y Lin, M Dohadwala, R K Batra, L Wu, J S Economou, S M Dubinett
• Journal: Human gene therapy (Hum Gene Ther) Vol. 11 Issue 1 Pg. 53-65 (Jan 01 2000) ISSN: 1043-0342 [Print] United States
• PMID: 10646639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-7

Topics

• Adenoviridae (genetics)
• Animals
• Dendritic Cells (immunology)
• Female
• Genetic Therapy
• Immunotherapy
• Injections, Intralesional
• Interleukin-7 (administration & dosage, genetics)
• Lung Neoplasms (immunology, therapy)
• Lymph Nodes (immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Remission Induction
• Spleen (immunology)