Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication.
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.
Miller
P W
PW
Department of Medicine, UCLA School of Medicine and West Los Angeles VA Medical Center, CA 90073, USA.
Sharma
S
S
Stolina
M
M
Butterfield
L H
LH
Luo
J
J
Lin
Y
Y
Dohadwala
M
M
Batra
R K
RK
Wu
L
L
Economou
J S
JS
Dubinett
S M
SM
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015316:Genetic Therapy; D007167:Immunotherapy; D015552:Injections, Intralesional; D015851:Interleukin-7 / Q000008:administration & dosage / Q000235:genetics*; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012074:Remission Induction; D013154:Spleen / Q000276:immunology
D015851:Interleukin-7