PMID- 35229644
OWN - NLM
STAT- MEDLINE
DCOM- 20220615
LR  - 20220621
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Linking)
VI  - 33
IP  - 11-12
DP  - 2022 Jun
TI  - The Effect of Rapamycin and Ibrutinib on Antibody Responses to Adeno-Associated 
      Virus Vector-Mediated Gene Transfer.
PG  - 614-624
LID - 10.1089/hum.2021.258 [doi]
AB  - Adeno-associated virus (AAV) vector-mediated gene transfer is lessening the 
      impact of monogenetic disorders. Human AAV gene therapy recipients commonly mount 
      immune responses to AAV or the encoded therapeutic protein, which requires 
      transient immunosuppression. Most efforts to date have focused on blunting AAV 
      capsid-specific T cell responses, which have been implicated in elimination of 
      AAV-transduced cells. Here, we explore the use of immunosuppressants, rapamycin 
      given alone or in combination with ibrutinib to inhibit AAV vector- or transgene 
      product-specific antibody responses. Our results show that rapamycin or ibrutinib 
      given alone reduces primary antibody responses against AAV capsid, but the 
      combination of rapamycin and ibrutinib is more effective, blunts recall 
      responses, and reduces numbers of circulating antibody-secreting plasma cells. 
      The drugs fail to lower B cell memory formation or to reduce the inhibitory 
      effects of pre-existing AAV capsid-specific antibodies on transduction 
      efficiency.
FAU - Xiang, Zhiquan
AU  - Xiang Z
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Kuranda, Klaudia
AU  - Kuranda K
AD  - Spark Therapeutics, Philadelphia, Pennsylvania, USA.
FAU - Quinn, William
AU  - Quinn W
AD  - Spark Therapeutics, Philadelphia, Pennsylvania, USA.
FAU - Chekaoui, Areski
AU  - Chekaoui A
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Ambrose, Robert
AU  - Ambrose R
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Hasanpourghai, Mohadeseh
AU  - Hasanpourghai M
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Novikov, Mikhail
AU  - Novikov M
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Newman, Dakota
AU  - Newman D
AUID- ORCID: 0000-0002-3835-0853
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Cole, Christina
AU  - Cole C
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Zhou, Xiangyang
AU  - Zhou X
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
FAU - Mingozzi, Federico
AU  - Mingozzi F
AD  - Spark Therapeutics, Philadelphia, Pennsylvania, USA.
FAU - Ertl, Hildegund C J
AU  - Ertl HCJ
AUID- ORCID: 0000-0001-9795-5206
AD  - Wistar Institute, Philadelphia, Pennsylvania, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220504
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Capsid Proteins)
RN  - 0 (Piperidines)
RN  - 1X70OSD4VX (ibrutinib)
RN  - JAC85A2161 (Adenine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenine/analogs & derivatives
MH  - Antibody Formation
MH  - Capsid Proteins/genetics
MH  - *Dependovirus/metabolism
MH  - Gene Transfer Techniques
MH  - Genetic Therapy
MH  - *Genetic Vectors/genetics
MH  - Humans
MH  - Piperidines
MH  - Sirolimus/pharmacology/therapeutic use
OTO - NOTNLM
OT  - AAV
OT  - antibody responses
OT  - gene transfer
OT  - ibrutinib
OT  - rapamycin
EDAT- 2022/03/02 06:00
MHDA- 2022/06/16 06:00
CRDT- 2022/03/01 08:41
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/06/16 06:00 [medline]
PHST- 2022/03/01 08:41 [entrez]
AID - 10.1089/hum.2021.258 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2022 Jun;33(11-12):614-624. doi: 10.1089/hum.2021.258. Epub 2022 
      May 4.