TY - JOUR
T1 - Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-Naïve Donors and Target a Range of Viral Epitopes
T2 - Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation
AU - Patel, Shabnum
AU - Lam, Sharon
AU - Cruz, Conrad Russell
AU - Wright, Kaylor
AU - Cochran, Christina
AU - Ambinder, Richard F.
AU - Bollard, Catherine M.
N1 - Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure human immunodeficiency virus (HIV) by eliminating infected recipient cells, particularly in the context of technologies that may confer HIV resistance to these stem cells. But, to date, the Berlin patient remains the only case of HIV cure despite multiple attempts to eradicate infection with HSCT. One approach to improve this is to administer virus-specific T cells, a strategy that has proven success in preventing other infections after transplantation. Although we have reported that broadly HIV–specific T cells can be expanded from HIV+ patients, allogeneic transplantations only contain virus-naïve T cells. Modifying this approach for the allogeneic setting requires a robust, reproducible platform that can expand HIV-specific cells from the naïve pool. Hence, we hypothesized that HIV-specific T cells could be primed ex vivo from seronegative individuals to effectively target HIV. Here, we show that ex vivo–primed and expanded HIV-specific T cells released IFNγ in response to HIV antigens and that these cells have enhanced ability to suppress replication in vitro. This is the first demonstration of ex vivo priming and expansion of functional, multi-HIV antigen–specific T cells from HIV-negative donors, which has implications for use of allogeneic HSCT as a functional HIV cure.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially cure human immunodeficiency virus (HIV) by eliminating infected recipient cells, particularly in the context of technologies that may confer HIV resistance to these stem cells. But, to date, the Berlin patient remains the only case of HIV cure despite multiple attempts to eradicate infection with HSCT. One approach to improve this is to administer virus-specific T cells, a strategy that has proven success in preventing other infections after transplantation. Although we have reported that broadly HIV–specific T cells can be expanded from HIV+ patients, allogeneic transplantations only contain virus-naïve T cells. Modifying this approach for the allogeneic setting requires a robust, reproducible platform that can expand HIV-specific cells from the naïve pool. Hence, we hypothesized that HIV-specific T cells could be primed ex vivo from seronegative individuals to effectively target HIV. Here, we show that ex vivo–primed and expanded HIV-specific T cells released IFNγ in response to HIV antigens and that these cells have enhanced ability to suppress replication in vitro. This is the first demonstration of ex vivo priming and expansion of functional, multi-HIV antigen–specific T cells from HIV-negative donors, which has implications for use of allogeneic HSCT as a functional HIV cure.
KW - Adoptive immunotherapy
KW - Human immunodeficiency virus
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UR - http://www.scopus.com/inward/citedby.url?scp=85009444421&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2015.12.007
DO - 10.1016/j.bbmt.2015.12.007
M3 - Article
C2 - 26721209
AN - SCOPUS:85009444421
SN - 1083-8791
VL - 22
SP - 536
EP - 541
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -