PMID- 34529177
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220223
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 23
IP  - 6
DP  - 2021 Sep 16
TI  - Evaluation of the Humoral Response to Adeno-Associated Virus-Based Gene Therapy 
      Modalities Using Total Antibody Assays.
PG  - 108
LID - 10.1208/s12248-021-00628-3 [doi]
LID - 108
AB  - The number of viral vector-based gene therapies (GTx) continues to grow with two 
      products (Zolgensma(R) and Luxturna(R)) approved in the USA as of March 2021. To 
      date, the most commonly used vectors are adeno-associated virus-based (AAV). The 
      pre-existing humoral immunity against AAV (anti-AAV antibodies) has been well 
      described and is expected as a consequence of prior AAV exposure. Anti-AAV 
      antibodies may present an immune barrier to successful AAV transduction and hence 
      negatively impact clinical efficacy and may also result in adverse events (AEs) 
      due to the formation of large immune complexes. Patients may be screened for the 
      presence of anti-AAV antibodies, including neutralizing (NAb) and total binding 
      antibodies (TAb) prior to treatment with the GTx. Recommendations for the 
      development and validation of anti-AAV NAb detection methods have been presented 
      elsewhere. This manuscript covers considerations related to anti-AAV 
      TAb-detecting protocols, including the advantages of the use of TAb methods, 
      selection of assay controls and reagents, and parameters critical to monitoring 
      assay performance. This manuscript was authored by a group of scientists involved 
      in GTx development representing eleven organizations. It is our intent to provide 
      recommendations and guidance to industry sponsors, academic laboratories, and 
      regulatory agencies working on AAV-based GTx viral vector modalities with the 
      goal of achieving a more consistent approach to anti-AAV TAb assessment. 
      Graphical abstract.
CI  - (c) 2021. American Association of Pharmaceutical Scientists.
FAU - Gorovits, Boris
AU  - Gorovits B
AUID- ORCID: 0000-0001-9405-7718
AD  - Sana Biotechnology, Inc., Cambridge, Massachusetts, USA. boris.gorovits@sana.com.
FAU - Azadeh, Mitra
AU  - Azadeh M
AD  - Alkermes, Waltham, Massachusetts, USA.
FAU - Buchlis, George
AU  - Buchlis G
AD  - University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Harrison, Travis
AU  - Harrison T
AD  - Precision for Medicine, Bethesda, Maryland, USA.
FAU - Havert, Mike
AU  - Havert M
AD  - bluebird bio, Cambridge, Massachusetts, USA.
FAU - Jawa, Vibha
AU  - Jawa V
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Long, Brian
AU  - Long B
AD  - BioMarin Pharmaceutical Inc., Novato, California, USA.
FAU - McNally, Jim
AU  - McNally J
AD  - BioAgilytix, Durham, North Carolina, USA.
FAU - Milton, Mark
AU  - Milton M
AD  - Novartis, Cambridge, Massachusetts, USA.
FAU - Nelson, Robert
AU  - Nelson R
AD  - Covance by Labcorp, Geneva, Switzerland.
FAU - O'Dell, Mark
AU  - O'Dell M
AD  - Covance by Labcorp, Indianapolis, Indiana, USA.
FAU - Richards, Karen
AU  - Richards K
AD  - Precision for Medicine, Bethesda, Maryland, USA.
FAU - Vettermann, Christian
AU  - Vettermann C
AD  - BioMarin Pharmaceutical Inc., Novato, California, USA.
FAU - Wu, Bonnie
AU  - Wu B
AD  - Johnson & Johnson, Spring House, Pennsylvania, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210916
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing/immunology
MH  - Antibodies, Viral/immunology
MH  - Dependovirus/genetics/*immunology
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/immunology
MH  - Humans
MH  - Immunity, Humoral/*immunology
PMC - PMC8445016
OTO - NOTNLM
OT  - adenovirus associated virus
OT  - gene therapy
OT  - immunogenicity
OT  - total anti-GTx antibody
COIS- The authors are employed by and receive compensation from companies that are 
      involved in development of gene therapy modality therapeutics and are listed on 
      the title page of the manuscript. The authors have no other relevant affiliations 
      or financial involvements with any organization or entity with a financial 
      interest in or financial conflict with the subject matter or materials discussed 
      in the manuscript apart from those disclosed. No writing assistance was utilized 
      in the production of this manuscript.
EDAT- 2021/09/17 06:00
MHDA- 2022/02/24 06:00
PMCR- 2021/09/16
CRDT- 2021/09/16 12:29
PHST- 2021/05/24 00:00 [received]
PHST- 2021/07/23 00:00 [accepted]
PHST- 2021/09/16 12:29 [entrez]
PHST- 2021/09/17 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2021/09/16 00:00 [pmc-release]
AID - 10.1208/s12248-021-00628-3 [pii]
AID - 628 [pii]
AID - 10.1208/s12248-021-00628-3 [doi]
PST - epublish
SO  - AAPS J. 2021 Sep 16;23(6):108. doi: 10.1208/s12248-021-00628-3.