Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Gene therapy with recombinant adenovirus (rAd) in humans: virological follow-up of patients and medical staff included in the French phase I study (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol; 16:A1555 1997. Unique Identifier : AIDSLINE ICDB/98643555 Gautier E; Saulnier P; Farace F; LeCesne A; Opolon P; Zitvogel L; Escudier B; Schatz C; Courtney M; LeChevalier T; Tancrede C; Tursz T; Roussy IG; Villejuif and Laboratoire Transgene, Strasbourg, France
Abstract:
In our gene therapy program evaluating the local delivery of therapeutic genes by rAd, 10 patients (pts) (3 at 10(7) and 10(8), 4 at 10(9) pfu) have now been included in the phase I study of intratumoral administration of a rAd-betaGAL in lung cancer. One of the main objectives was to evaluate the safety of rAd-betaGAL administration for both pts and medical staff (MS). Methods: Absence of wild type (wt) Ad was checked in the throat and stool of both pts and MS before rAd administration (or exposure). Presence of rAd was controlled in pts every 2 days on week 1 and then monthly after rAd injection, in the blood, throat, sputum, urine, stool, and in bronchoalveolar lavages (BAL) at each bronchoscopy. Culture cell and PCR analysis were performed on each specimen. AntiAd antibodies (Ad-Ab) were measured by complement fixation assay (CF) and hemagglutination inhibition assay (HI) before and monthly after rAd administration (pts) or exposure (MS). Results: One pt was not injected because of wt Ad on throat specimen. Viral culture of BAL and blood samples taken immediately after rAd-betaGAL injection were respectively positive in all pts and in 2 pts receiving 10(9) pfu. PCR analysis of sputum and throat specimen were positive in all pts within the first 13 days after rAd injection. BAL samples remained positive at 3 months in 4 pts after rAd-betaGAL injection. 6 pts had a significant rise in their Ad-Ab titer (CF and HI). 3/4 pts receiving 10(9) pfu had a huge anti betaGal response (Elisa). Strong cellular (proliferative and cytotoxic) anti-betaGAL responses were observed in 3/4 pts at the 10(9) pfu level. Expression of betaGAL was observed in 7/10 tumor biopsies. All 673 samples (throat and stools) taken from 72 MS before and after injection of each pt were negative for wt Ad and rAd-betaGAL. None of the 373 sera samples exhibited a rise in Ad-Ab (CF). Conclusions: This study confirms that a marker gene can be safely introduced into human tumor cells using a rAd, for both pts and MS. Final data will be presented.
Keywords: Adenoviridae/*GENETICS/ISOLATION & PURIF Bronchoalveolar Lavage Fluid Enzyme-Linked Immunosorbent Assay Follow-Up Studies *Gene Therapy *Genetic Vectors Human Viral Load ABSTRACT CLINICAL TRIAL CLINICAL TRIAL, PHASE I 980228
M9820747
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
