3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

IMMUNE THERAPY OF ADVANCED HIV-1 INFECTION BY TRANSDUCED AUTOLOGOUS T HELPER CELLS EXPRESSING A PEPTIDE WHICH INHIBITS VIRAL ENTRY. RESULTS OF A PHASE I PILOT STUDY

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuOa0202

van Lunzen J.¹, Glaunsinger T.¹, Stahmer I.¹, Kühlcke K.², Schilz A.², Stellbrink H.J.¹, Mayr C.³, Dinauer N.⁴, Alexandrov A.⁴, von Laer D.^5
1University Medical Center Eppendorf, Hamburg, Germany, ²EUFETS AG, Idar-Oberstein, Germany, ³Private Practice Seestrasse, Berlin, Germany, ⁴Fresenius Biotech AG, Bad Homburg, Germany, ⁵Georg-Speyer-Haus, Frankfurt, Germany

INTRODUCTION: Despite significant improvements of HAART, limitations such as drug resistance and toxicities call for innovative strategies.

OBJECTIVE: To develop an effective HIV gene therapy involving the ex vivo transfer of an antiviral gene into autologous CD4+ T cells.

METHODS: A novel antiviral gene (M87o) was cloned into a retroviral vector backbone inhibiting virus entry by expressing a membrane anchored peptide derived from the second heptad repeat of gp41. Autologous T cells obtained by lymphapheresis were expanded ex vivo and transfected. Gene modified CD4+ T cells were transfused into pts. with advanced disease (CD4 <200/µl) and failing HAART (VL >5000 c/mL) due to MDR viruses and followed in vivo by qPCR in LN and PB.

RESULTS: M87o inhibited virus entry for all HIV isolates tested with 99-100% efficiency. A median of 1.26 × 10⁹ transfected T cells were retransfused into 10 pts. with advanced disease (median CD4 93/µl, VL 4.96 log₁₀ c/mL). No severe side effects or grade 3-4 AE's occurred. Transduced T cells enriched in the PB immediately after retransfusion leading to a gene marking of 20% of peripheral CD4+ T cells. Rapid redistribution to LN was observed where transduced T cells could be detected up to 9 mths. In 6/10 pts. a significant increase (>50%) of CD4 counts was observed despite unchanged HAART. Mean relative increase at week 12 was 43% compared to baseline (110/µl to 153/µl) with no significant changes of VL. A positive correlation between the absolute number of transfected CD4 T cells and increases of CD4 counts was observed.

CONCLUSIONS: This first gene therapeutic approach for HIV infection based on entry inhibition shows promising results. Transduced CD4+ T cells have been transfused safely leading to an increase of circulating CD4+ T cells. This increase in app. 60% of these advanced patients warrant further trials in less immunocompromised cohorts.

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Clinical | TuOa0202 | Jan Van Lunzen
12.8 508 12.8 Immune therapy

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