HIV-specific, ex vivo expanded T cell therapy (HXTC) for HIV clearance: feasibility, safety and efficacy
Supplement : Abstracts of the IAS HIV Cure and Cancer Forum 2017Journal of Virus Eradication 2017; 3 supplement 1
Abstract No : 24
Julia M. Sung1, JoAnn D. Kuruc1, Matthew Clohosey1, Amanda Crooks1, Shabnum Patel2, Lauren Roesch2, Patrick Hanley2, C. Russell Cruz2, Nancie Archin1, Joseph J. Eron1, Nilu Goonetilleke1, Cliona M. Rooney3, Catherine M. Bollard2, David M. Margolis1, Cynthia L. Gay1
1UNC HIV Cure Center, University of North Carolina at Chapel Hill,NC,USA, 2Center for Cancer and Immunology Research, Children's National Health System,Washington DC,USA, 3Department of Molecular Virology and Microbiology, Department of Immunology, Section of Hematology-Oncology, Baylor College of Medicine,Houston, TX,USA
Adoptive T cell therapy has had dramatic successes in oncology in the treatment of EBV-related malignancies and viral infections following hematopoietic stem cell transplantation. We adapted this method to produce ex-vivo expanded HIV-specific T cells (HXTCs) as part of an HIV cure strategy.
This is a Phase 1, proof of concept study (NCT02208167) of the administration of HXTCs to antiretroviral (ART) suppressed, HIV-infected participants. T cells were stimulated ex vivo with autologous dendritic cells pulsed with overlapping Clade B consensus peptides spanning the regions of Gag, Pol and Nef. Participants received two HXTC infusions, 2×107 cells/m2 each, 2 weeks apart. Leukapheresis was performed at baseline and 12 weeks post-infusion to measure the frequency of resting cell infection by the Quantitative Viral Outgrowth Assay (QVOA), and antiviral capacity of CD8 T cells was evaluated pre- and post-infusion.
Six participants received two biweekly infusions of HXTCs. Composition of the HXTC product was heterogeneous across participants: overall cells were predominantly CD8+ T cells, although three participants had greater than 20% NK cells. Gag, Pol or Nef specificity ranged from below the limit of detection to over 800 SFU/105 cells in IFNγ Elispot; all HXTC products demonstrated specificity to at least one peptide pool. HXTCs were well tolerated, with only Grade 1 treatment related AEs. A modest increase in antiviral capacity was detected following HXTC infusion in two participants, but overall there was no change in antiviral capacity across all participants. The significance, if any, of this finding in the two participants remains unclear. As expected, in the absence of a latency reversing agent, no meaningful decline in the frequency of resting CD4 T cell infection was detected.
HXTC therapy in ART-suppressed, HIV-infected individuals appears safe and well-tolerated, with no induction of clinically perceptible signs of immune activation, perhaps due to the low HIV antigen burden expressed during ART. Detection of an expanded HIV-specific immune response remains a challenge in the absence of lymphodepletion and/or antigen exposure with latency reversal. Evaluation of HXTC therapy in combination with latency reversal is underway.