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: Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Allogeneic HSCT can potentially cure 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 post-transplant. While we have reported that broadly-HIV-specific T cells can be expanded from HIV+ patients, allogeneic transplants only contain virus-naïve T cells. Modifying this approach for the allogeneic setting thus required 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.

Attitudes and Willingness to Assume Risk of Experimental Therapy to Eradicate Genital Herpes Simplex Virus Infection

“…While cure of chronic viral infections seemed improbable several years ago, HIV cure is currently an active research area with several investigational approaches, and at least one patient has been cured following hematopoietic stem cell transplantation (5–9). An assessment in HIV-1 seropositive individuals in the United Kingdom showed high interest in HIV-1 cure studies, and willingness to take experimental therapies in the absence of personal benefit (10).…”

T cells for viral infections after allogeneic hematopoietic stem cell transplant

“…HIV-specific T cells manufactured this way are currently being evaluated in the autologous setting (#NCT02208167) and studies utilizing donor-derived HIV-specific T cells after allogeneic HSCT are planned. 79 An alternative approach in the naïve donor is to transduce T cells with a TCR with known viral specificity. 80,81 Although this strategy offers a novel, rapid method to generate VSTs from naïve donors, it does impose the additional cost and regulatory requirements of gene transfer.…”

Reprint of: Virus-Specific T Cells: Broadening Applicability

“…Autologous multiepitope-specific T cells are now in an ongoing clinical trial (NCT02208167). Another study demonstrated that multiepitope-specific T cells can be generated from HIV-naïve donors, opening up the possibility of antiviral T cell therapy in HIV + individuals with hematologic malignancies necessitating allogeneic HSCT [30].…”