Targeting of products of genes to tumor sites using adoptively transferred A-NK and T-LAK cells.
Despite successes in animals, cytokine gene expression selectively in human tumors is difficult to achieve owing to lack of efficient delivery methods. Since interleukin (IL)-2-activated natural killer (A-NK) and phytohemagglutinin and IL-2 activated killer T (T-LAK) cells, as previously demonstrated, localize and accumulate in murine lung tumor metastases following adoptive transfer, we transduced them to test their ability to deliver products of genes selectively to tumors. Assessments of transduction efficiency in vitro demonstrated that adenoviral transduction consistently resulted in high (>60%) transduction rates and substantial expression of transgenes such as GFP, Red2, luciferase, beta-galactosidase and mIL-12 for at least 4 days. In vivo experiments illustrated that Ad-GFP transduced A-NK and Ad-Red2 (RFP) transduced T-LAK or mIL-12 transduced A-NK cells localized 10-50-fold more or survived significantly better than mock transduced cells, respectively, within lung metastases than in the surrounding normal lung tissue. Most importantly, mIL-12 transduced A-NK cells provided a significantly greater antitumor response than non-transduced A-NK cells. Thus, adoptive transfer of A-NK and T-LAK cells represents an efficient method for targeting products of genes to tumor sites.
Goding
S
S
Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Yang
Q
Q
Mi
Z
Z
Robbins
P D
PD
Basse
P H
PH
D000256:Adenoviridae / Q000235:genetics; D019264:Adoptive Transfer; D000818:Animals; D005696:Galactosidases / Q000032:analysis / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000032:analysis; D018664:Interleukin-12 / Q000235:genetics*; D015979:Killer Cells, Lymphokine-Activated / Q000737:chemistry / Q000276:immunology / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology / Q000637:transplantation*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000637:transplantation*; D014161:Transduction, Genetic
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D008156:Luciferases; D005696:Galactosidases