Institute of Biomedical Sciences

Title

HIV-Specific T Cells Generated from HIV-Naive Adult and Cord Blood Donors Target a Range of Viral Epitopes' Implications for a Cure Strategy after Allogeneic Stem Cell Transplant

Poster Number

19

Document Type

Poster

Keywords

HIV-specific T cells, cord blood, HSCT, adoptive T cell therapy

Publication Date

4-2017

Abstract

Adoptive T cell therapy has been successful in boosting viral-specific immunity post-HSCT, preventing viral rebound of CMV and EBV. However, therapeutic use of T cells to boost HIV-specific T cell immunity in HIV+ patients has met limited success. Despite multiple attempts to eradicate HIV with allogeneic-HSCT, there is only one case of functional HIV cure. We hypothesized that broadly HIV-specific CD8 and CD4 T-cells (HXTCs) could be expanded from patients on ARVs, as well as HIV-negative adult and cord blood donors (dHXTC), employing a non–HLA restricted approach for the treatment of HIV+ individuals after autologous or allogeneic HSCT.

We have expanded autologous HXTCs from HIV+ subjects under NCT02208167. To extend this approach to the allogeneic HSCT setting, we generated dHXTCs from HIV-naive adults (n=9) and cord blood donors (n=11). IFNg-ELISPOT showed dHXTCs from adult donors were specific against Gag, Nef, and Pol (mean=220 IFNg SFC/1e5 cells) versus irrelevant antigen actin (mean=6 SFC/105cells)(n=9). Similarly, we are able to produce cord dHXTCs (n=11) that showed specificity to Gag (mean=78 SFC/105cells), Nef (mean=96 SFC/105cells), or Pol (mean=174 SFC/105cells), compared to CTL-only (mean=2 SFC/105cells) in IFNg-ELISPOT. dHXTCs were polyfunctional producing proinflammatory TNFα, IL2, IL6, IL8, and perforin responses (p

In summary, HIV-specific T cells can be expanded from HIV+ and HIVneg donors for clinical use. Focusing on donors with HLA types that are associated with well characterized HIV responses (e.g. HLA A02) or associated with delayed progression to AIDS (e.g.HLA B27, B51, B57) may allow us to identify HLA-restricted epitopes critical for the successful development of a potent HIV-specific T cell therapeutic. Hence, the administration of dHXTCs derived from naive donors could offer a unique curative strategy post-allogeneic stem cell transplant.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Comments

To be presented at GW Annual Research Days 2017.

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HIV-Specific T Cells Generated from HIV-Naive Adult and Cord Blood Donors Target a Range of Viral Epitopes' Implications for a Cure Strategy after Allogeneic Stem Cell Transplant

Adoptive T cell therapy has been successful in boosting viral-specific immunity post-HSCT, preventing viral rebound of CMV and EBV. However, therapeutic use of T cells to boost HIV-specific T cell immunity in HIV+ patients has met limited success. Despite multiple attempts to eradicate HIV with allogeneic-HSCT, there is only one case of functional HIV cure. We hypothesized that broadly HIV-specific CD8 and CD4 T-cells (HXTCs) could be expanded from patients on ARVs, as well as HIV-negative adult and cord blood donors (dHXTC), employing a non–HLA restricted approach for the treatment of HIV+ individuals after autologous or allogeneic HSCT.

We have expanded autologous HXTCs from HIV+ subjects under NCT02208167. To extend this approach to the allogeneic HSCT setting, we generated dHXTCs from HIV-naive adults (n=9) and cord blood donors (n=11). IFNg-ELISPOT showed dHXTCs from adult donors were specific against Gag, Nef, and Pol (mean=220 IFNg SFC/1e5 cells) versus irrelevant antigen actin (mean=6 SFC/105cells)(n=9). Similarly, we are able to produce cord dHXTCs (n=11) that showed specificity to Gag (mean=78 SFC/105cells), Nef (mean=96 SFC/105cells), or Pol (mean=174 SFC/105cells), compared to CTL-only (mean=2 SFC/105cells) in IFNg-ELISPOT. dHXTCs were polyfunctional producing proinflammatory TNFα, IL2, IL6, IL8, and perforin responses (p

In summary, HIV-specific T cells can be expanded from HIV+ and HIVneg donors for clinical use. Focusing on donors with HLA types that are associated with well characterized HIV responses (e.g. HLA A02) or associated with delayed progression to AIDS (e.g.HLA B27, B51, B57) may allow us to identify HLA-restricted epitopes critical for the successful development of a potent HIV-specific T cell therapeutic. Hence, the administration of dHXTCs derived from naive donors could offer a unique curative strategy post-allogeneic stem cell transplant.