Title

Advances in gene therapy (HIV Cure & Gene Therapy Forum)

Code

SY18

Session Type

Symposium

Track

Not applicable

Channel

IAS+

Date Time

19 July 11:00- 12:00

Local Date Time

11:00 - 12:00 W. Europe Daylight Time

Co-Chairs:

Jessica SALZWEDEL, AVAC, United States
Chris PETERSON, Fred Hutchinson Cancer Research Center, United States

In honour of the late Timothy Ray Brown, the Berlin Patient, session 1 of the HIV Cure & Gene Therapy Forum will include a commemoration followed by talks that will showcase exciting advances in cell and gene therapy for HIV that are being informed by analogous efforts in other areas, including cancer, hemoglobinopathies, and hemophilia.

1 min	Co-chairs introduction Chris PETERSON, Fred Hutchinson Cancer Research Center, United States Jessica SALZWEDEL, AVAC, United States

10 min	Remembrance of Timothy Ray Brown Erick SEELBACH, Pierce County AIDSFoundation, United States Nichole KLATT, University of Minnesota, United States

12 min	In vivo targeting with AAV and applications to perinatal HIV infection Mauricio MARTINS, Scripps Research, United States

12 min	Ex vivo targeting of hematopoietic stem cells in the setting of hemoglobinopathies and HIV Scott KITCHEN, David Geffen School of Medicine, UCLA, United States

12 min	Engineering T cells against HIV and malignancies Carl JUNE, University of Pennsylvania Perelman School of Medicine, United States

11 min	Engineering CD4 Tscm cells to be resistant to HIV Joumana ZEIDAN, Canada	PDF

AUTHOR

Mayte Coiras

SUMMARY

This session contained an emotive remembrance of Thimothy Ray Brown, the so-called Berlin patient, followed by the latest advances in cell and gene therapy against HIV. Improved ways to deliver HIV antibodies through rAAV vectors and new engineered T cells to bolster endogenous immune responses are presented.

HIGHLIGHTS

Mauricio Martins gives hope about the safe, improved delivery of bNAbs against HIV with recombinant AAV in baby monkeys. Sustained expression of 3BNC117 provided protection after oral challenge and it was assesed for at least 2 years, which may permit covering standard breastfeeding period. Scott Kitchen has shown new advances about how immunity may be engineered to reprogramme cells with CARs, using HSC instead of T cells that are long lived and may be engrafted to provide unlimited T cells reprogrammed to target HIV-infected cells. Carl June showed interim results of pilot study NCT03617198 to evaluate if treatment with autologous T cells with CCR5 disrupted by ZFN SB-728mR and CD4 CAR is safe and effective to block HIV entry into CD4. Response is varied among patients but ATI after 8 weeks of engraftment looks promising. Finally, Joumana Zaidan also highlights the importance of CCR5 gene editing of autologous CD4+ T cells as a safe and accesible therapeutic intervention to target HIV reservoir by describing RARO cells, which are CD4 Tscm cells expressing CD45RA/RO that may regenerate and then persist 5y post-infusion, providing post-ART control.

CRITICAL ASSESSMENT

Encouraging results that bring us closer to the goal of using gene therapy to maintain control of viral replication in the absence of ART by inducing the sustained synthesis of bNAbs after rAAV delivery. New methods for CAR engineering are also been explored, trying to get the better options for a sustained delivery of T cells specifically directed against HIV-infected cells. No significant adverse effects have been detected, but long term activity is still elusive. Engineering may be used not only to protect CD4 T cells, but also to bolster CD8 responses.