Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants.
Rapid production of protein-based tumor-specific vaccines for the treatment of malignancies is possible with the plant-based transient expression system described here. We created a modified tobamoviral vector that encodes the idiotype-specific single-chain Fv fragment (scFv) of the immunoglobulin from the 38C13 mouse B cell lymphoma. Infected Nicotiana benthamiana plants contain high levels of secreted scFv protein in the extracellular compartment. This material reacts with an anti-idiotype antibody by Western blotting, ELISA, and affinity chromatography, suggesting that the plant-produced 38C13 scFv protein is properly folded in solution. Mice vaccinated with the affinity-purified 38C13 scFv generate >10 micrograms/ml anti-idiotype immunoglobulins. These mice were protected from challenge by a lethal dose of the syngeneic 38C13 tumor, similar to mice immunized with the native 38C13 IgM-keyhole limpet hemocyanin conjugate vaccine. This rapid production system for generating tumor-specific protein vaccines may provide a viable strategy for the treatment of non-Hodgkin's lymphoma.
McCormick
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Biosource Technologies, Inc., 3333 Vacavalley Parkway, Suite 1000, Vacaville, CA 95688, USA.
Kumagai
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MH
Hanley
K
K
Turpen
T H
TH
Hakim
I
I
Grill
L K
LK
Tusé
D
D
Levy
S
S
Levy
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D018506:Gene Expression Regulation, Plant / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006031:Glycosylation; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010940:Plant Proteins / Q000032:analysis; D010947:Plants, Toxic; D014026:Nicotiana / Q000235:genetics* / Q000276:immunology; D017898:Tobamovirus / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use
D000939:Epitopes; D007128:Immunoglobulin Fragments; D010940:Plant Proteins; D014612:Vaccines