Targeting foreign major histocompatibility complex molecules to tumors by tumor cell specific single chain antibody (scFv).
Down-regulation of the major histocompatibility complex (MHC) is one of the major mechanisms that tumor cells adopted to escape immunosurveillance. Therefore, specifically coating tumor cells with foreign MHC may make tumor cells a better target for immune recognition and surveillance. In this study, we designed and generated a fusion protein, H2Kd/scPSMA, consisting of a single chain antibody against human prostate specific membrane antigen (PSMA) and the extracellular domain of mouse H-2Kd. The expression of this fusion protein in B16F0 mouse melanoma cells was confirmed by RT-PCR and fluorescent activated cell sorting (FACS). Our animal study showed that the expression of H2Kd/scPSMA in B16F0/PSMA5, a B16F0 cell line expressing human PSMA, significantly inhibited tumor growth as demonstrated in the pulmonary metastasis assay and tumor growth study and improved overall survival.
Li
Jinhua
J
Oncology Research Institute, Greenville Hospital System, Greenville, SC 29605, USA.
Franek
Karl J
KJ
Patterson
Andrea L
AL
Holmes
Lillia M
LM
Burgin
Kelly E
KE
Ji
Jianfei
J
Yu
Xianzhong
X
Wagner
Thomas E
TE
Wei
Yanzhang
Y
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry; D002455:Cell Division; D002469:Cell Separation; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005821:Genetic Techniques; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D008175:Lung Neoplasms / Q000556:secondary; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D000954:Antigens, Surface; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II