Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-03-02

AUTHORS

Takahito Masuda, Hiroshi Fujimoto, Ryotaro Teranaka, Masayuki Kuroda, Yasuyuki Aoyagi, Takeshi Nagashima, Takafumi Sangai, Mamoru Takada, Ayako Nakagawa, Yoshitaka Kubota, Koutaro Yokote, Masayuki Ohtsuka

ABSTRACT

PurposeAlthough recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect.MethodsPlasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2−) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states.ResultsAnti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model.ConclusionsHER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies. More... »

PAGES

625-634

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-020-05581-x

DOI

http://dx.doi.org/10.1007/s10549-020-05581-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1125320876

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32124135


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33 schema:description PurposeAlthough recent advances in molecular target therapy have improved the survival of breast cancer patients, high cost and frequent hospital visits result in both societal and individual burden. To reduce these problems, it has been proposed to produce antibodies in vivo. Here, we constructed gene-transduced human ceiling culture-derived proliferative adipocytes secreting anti-HER2 antibody (HER2-ccdPAs) and evaluated their ability to secrete antibody and mediate an anti-tumor effect.MethodsPlasmid lentivirus was used as a recipient for anti-HER2 antibody cDNA and transduced into human proliferative adipocyte. Secretory antibody expression was evaluated by ELISA and western blot. Specific binding of secretory antibody to HER2 was examined by immunofluorescence analysis. Direct and indirect anti-tumor effects of supernatants from HER2-ccdPAs were evaluated using BT474 (HER2+) and MDA-MB-231 (HER2−) breast cancer cell lines. Additionally, whether adipocyte differentiation affects antibody secretion was investigated using supernatant collected from different cell maturation states.ResultsAnti-HER2 antibody was identified in the supernatant from HER2-ccdPAs and its production increased with the differentiation into mature adipocyte. Antibodies in supernatants from HER2-ccdPAs bound to HER2-positive breast cancer cells similar to trastuzumab. Supernatant from HER2-ccdPAs inhibited the proliferation of BT474 but not MDA-MB-231 cells, and downregulated AKT phosphorylation in BT474 cells compared with controls. Supernatants from HER2-ccdPAs also had an indirect anti-tumor effect on BT474 cells through ADCC. Additionally, Single inoculation of HER2-ccdPAs showed an anti-tumor effect in BT474 xenograft model.ConclusionsHER2-ccdPAs might be useful for cell-based gene therapy. This system could be a platform for various antibody therapies.
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40 Akt phosphorylation
41 BT474
42 ELISA
43 HER2
44 HER2-positive breast cancer
45 HER2-positive breast cancer cells
46 MDA-MB-231 breast cancer cell lines
47 MDA-MB-231 cells
48 Western blot
49 ability
50 adipocyte differentiation
51 adipocytes
52 advances
53 analysis
54 anti-HER2 antibody
55 anti-HER2 antibody therapy
56 anti-tumor effects
57 antibodies
58 antibody cDNA
59 antibody expression
60 antibody secretion
61 antibody therapy
62 binding
63 blot
64 breast cancer
65 breast cancer cell lines
66 breast cancer cells
67 breast cancer patients
68 burden
69 cDNA
70 cancer
71 cancer cell lines
72 cancer cells
73 cancer patients
74 cell lines
75 cell maturation state
76 cell-based gene therapy
77 cells
78 control
79 cost
80 differentiation
81 effect
82 expression
83 frequent hospital visits
84 gene therapy
85 high cost
86 hospital visits
87 immunofluorescence analysis
88 indirect anti-tumor effects
89 individual burden
90 inoculation
91 lentivirus
92 lines
93 maturation state
94 model
95 molecular target therapy
96 patients
97 phosphorylation
98 platform
99 problem
100 production
101 proliferation
102 recent advances
103 recipients
104 secretion
105 secretory antibodies
106 single inoculation
107 specific binding
108 state
109 supernatant
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115 visits
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