Chronic Delivery of Antibody Fragments Using Immunoisolated Cell Implants as a Passive Vaccination Tool

被引：27

作者：

Belaunzaran, Osiris Marroquin ^{[1
]}

Cordero, Maria Isabel ^{[2
]}

Setola, Veronica ^{[1
]}

Bianchi, Siro ^{[3
]}

Galli, Carmela ^{[3
]}

Bouche, Nicolas ^{[1
]}

Mlynarik, Vladimir ^{[4
]}

Gruetter, Rolf ^{[4
]}

Sandi, Carmen ^{[2
]}

Bensadoun, Jean-Charles ^{[1
]}

Molinari, Maurizio ^{[3
]}

Aebischer, Patrick ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Brain Mind Inst, Neurodegenerat Studies Lab, Lausanne, Switzerland

[2] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Behav Genet, Lausanne, Switzerland

[3] Inst Biomed Res, Bellinzona, Switzerland

[4] Ecole Polytech Fed Lausanne, Lab Funct & Metab Imaging, Lausanne, Switzerland

来源：

PLOS ONE | 2011年 / 6卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; ADENOASSOCIATED VIRUS; BETA IMMUNOTHERAPY; TRANSGENIC MOUSE; MICE; DEPOSITION; MODEL; ANGIOPATHY; IMPAIRMENT;

D O I：

10.1371/journal.pone.0018268

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. Methodology and Principal Findings: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Ab peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Ab peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. Conclusions and Significance: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.

引用

页数：11

共 38 条

[1] Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients [J].

Aebischer, P ;

Schluep, M ;

Deglon, N ;

Joseph, JM ;

Hirt, L ;

Heyd, B ;

Goddard, M ;

Hammang, JP ;

Zurn, AD ;

Kato, AC ;

Regli, F ;

Baetge, EE .

NATURE MEDICINE, 1996, 2 (06) :696-699

[2] Recombinant proteins for neurodegenerative diseases: the delivery issue [J].

Aebischer, P ;

Ridet, JL .

TRENDS IN NEUROSCIENCES, 2001, 24 (09) :533-540

[3] Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor:: Results of a phase I study [J].

Bloch, J ;

Bachoud-Lévi, AC ;

Déglon, N ;

Lefaucheur, JP ;

Winkel, L ;

Palfi, S ;

Nguyen, JP ;

Bourdet, C ;

Gaura, V ;

Remy, P ;

Brugières, P ;

Boisse, MF ;

Baudic, S ;

Cesaro, P ;

Hantraye, P ;

Aebischer, P ;

Peschanski, M .

HUMAN GENE THERAPY, 2004, 15 (10) :968-975

[4] Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid [J].

Calhoun, ME ;

Burgermeister, P ;

Phinney, AL ;

Stalder, M ;

Tolnay, M ;

Wiederhold, KH ;

Abramowski, D ;

Sturchler-Pierrat, C ;

Sommer, B ;

Staufenbiel, M ;

Jucker, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14088-14093

[5] Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Aβ deposits in APP+PS1 transgenic mice [J].

Carty, Niki C. ;

Nash, Kevin ;

Lee, Daniel ;

Mercer, Mary ;

Gottschall, Paul E. ;

Meyers, Craig ;

Muzyczka, Nicholas ;

Gordon, Marcia N. ;

Morgan, Dave .

MOLECULAR THERAPY, 2008, 16 (09) :1580-1586

[6] Therapeutic antibodies: successes, limitations and hopes for the future [J].

Chames, Patrick ;

Van Regenmortel, Marc ;

Weiss, Etienne ;

Baty, Daniel .

BRITISH JOURNAL OF PHARMACOLOGY, 2009, 157 (02) :220-233

[7] Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design [J].

Deyev, Sergey M. ;

Lebedenko, Ekaterina N. .

BIOESSAYS, 2008, 30 (09) :904-918

[8] Intravenous immunoglobulins containing antibodies against β-amyloid for the treatment of Alzheimer's disease [J].

Dodel, RC ;

Du, Y ;

Depboylu, C ;

Hampel, H ;

Frölich, L ;

Haag, A ;

Hemmeter, U ;

Paulsen, S ;

Teipel, SJ ;

Brettschneider, S ;

Spottke, A ;

Nölker, C ;

Möller, HJ ;

Wei, X ;

Farlow, M ;

Sommer, N ;

Oertel, WH .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2004, 75 (10) :1472-1474

[9] Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain [J].

Dovey, HF ;

John, V ;

Anderson, JP ;

Chen, LZ ;

Andrieu, PD ;

Fang, LY ;

Freedman, SB ;

Folmer, B ;

Goldbach, E ;

Holsztynska, EJ ;

Hu, KL ;

Johnson-Wood, KL ;

Kennedy, SL ;

Kholedenko, D ;

Knops, JE ;

Latimer, LH ;

Lee, M ;

Liao, Z ;

Lieberburg, IM ;

Motter, RN ;

Mutter, LC ;

Nietz, J ;

Quinn, KP ;

Sacchi, KL ;

Seubert, PA ;

Shopp, GM ;

Thorsett, ED ;

Tung, JS ;

Wu, J ;

Yang, S ;

Yin, CT ;

Schenk, DB ;

May, PC ;

Altstiel, LD ;

Bender, MH ;

Boggs, LN ;

Britton, TC ;

Clemens, JC ;

Czilli, DL ;

Dieckman-McGinty, DK ;

Droste, JJ ;

Fuson, KS ;

Gitter, BD ;

Hyslop, PA ;

Johnstone, EM ;

Li, WY ;

Little, SP ;

Mabry, TE ;

Miller, FD ;

Ni, B .

JOURNAL OF NEUROCHEMISTRY, 2001, 76 (01) :173-181

[10] Immunization in Alzheimer's disease: naive hope or realistic clinical potential? [J].

Foster, J. K. ;

Verdile, G. ;

Bates, K. A. ;

Martins, R. N. .

MOLECULAR PSYCHIATRY, 2009, 14 (03) :239-251

← 1 2 3 4 →