Gene gun application in the generation of effector T cells for adoptive immunotherapy.
We utilized the gene gun to transfect subcutaneous D5 melanoma and MT-901 mammary carcinoma tumors in situ with a granulocyte/macrophage-colony-stimulating factor (GM-CSF) plasmid complexed to gold particles. There was diminished tumor growth following bombardment with GM-CSF plasmid, which was apparent only during the period of administration. Transgenic GM-CSF was produced by the skin overlying the tumors and not by the tumors themselves. GM-CSF plasmid bombardment resulted in increased cell yields within tumor-draining lymph nodes (TDLN) with at least a 12-fold increase in the percentage of dendritic cells (8.9%) compared to controls (0. 7%). Secondarily activated TDLN cells from animals transfected with GM-CSF demonstrated enhanced cytokine release (interferon gamma, GM-CSF and interleukin-10) in response to tumor stimulator cells compared to controls, and had an increased capacity to mediate tumor regression in adoptive immunotherapy. There was a small, but detectable, non-specific immune adjuvant effect observed with gold particle bombardment alone, which was less than with GM-CSF plasmid. The adjuvant effect of GM-CSF plasmid required peri-tumoral transgene expression since gene bombardment away from the tumor was ineffective.
Tanigawa
K
K
Division of Surgical Oncology, University of Michigan, 3302 Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0932, USA.
Yu
H
H
Sun
R
R
Nickoloff
B J
BJ
Chang
A E
AE
D000818:Animals; D019470:Biolistics; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D006046:Gold; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014162:Transfection / Q000379:methods
D016207:Cytokines; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D006046:Gold; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor