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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1631-1638.
Prepublished online as a Blood First Edition Paper on July 8, 2004May 25, 2004; DOI 10.1182/blood-2004-01-0360.
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Submitted January 30, 2004
Accepted May 8, 2004
Adenovirus-mediated intralesional interferon- gene transfer induces tumor regressions in cutaneous lymphomas
Reinhard Dummer*, Jessica C Hassel, Friederike Fellenberg, Stefan Eichmueller, Tanja Maier, Philippe Slos, Bruce Acres, Pascal Bleuzen, Vincent Bataille, Patrick Squiban, Guenter Burg, and Mirjana Urosevic
Dermatology, University Hospital Zurich, Zurich, Switzerland
Skin Cancer Unit, German Cancer Research Center, Heidelberg, Germany
Transgene S.A., Strasbourg, France
* Corresponding author; email: Reinhard.Dummer{at}usz.ch.
Primary cutaneous lymphomas have been successfully treated with interferons (IFNs), counterbalancing the Th2-skewing state. We undertook a phase I, open-label, dose-escalating trial of repeated, intratumoral administration of TG1042 in patients with advanced primary cutaneous T cell lymphomas (CTCL) and multilesional cutaneous B cell lymphomas (CBCL). TG1042 is a third generation, non-replicating human adenovirus vector containing human IFN- cDNA insert. Nine patients (7 CTCL, 2 CBCL) were enrolled at the following TG1042 doses: 3x109, 3x1010, and 3x1011 total particles. Local clinical response was observed in 5/9 treated patients [3 patients with complete (CR) and 2 patients with partial response (PR)]. Out of these, 3 patients showed systemic CR, with the clearance of other non-injected skin lesions. Clinical response lasted for a median of 3 months (range 1-6 mo). Adverse events were mostly of grade 1 and 2. 7/9 treated patients had detectable TG1042-derived IFN- message in injected lesions after the first treatment cycle. TG1042-IFN- message was also detectable after several treatment cycles. We demonstrate the induction of humoral immune response to lymphoma tumor-antigen se70-2 posttreatment. Our study shows that intralesional injections of TG1042 are both safe and well tolerated.

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