Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas.

Abstract:

:Primary cutaneous lymphomas have been successfully treated with interferons (IFNs), counterbalancing the T-helper 2 (Th2)-skewing state. We undertook a phase 1, open-label, dose-escalating trial of repeated intratumoral administration of TG1042 in patients with advanced primary cutaneous T-cell lymphomas (CTCLs) and multilesional cutaneous B-cell lymphomas (CBCLs). TG1042 is a third-generation, nonreplicating human adenovirus vector containing a human IFN-gamma cDNA insert. Nine patients (7 CTCL, 2 CBCL) were enrolled at the following TG1042 doses: 3 x 10(9), 3 x 10(10), and 3 x 10(11) total particles. Local clinical response was observed in 5 of 9 treated patients (3 patients with complete response [CR] and 2 patients with partial response [PR]). Out of these, 3 patients showed systemic CR with the clearance of other noninjected skin lesions. Clinical response lasted for a median of 3 months (range, 1-6 months). Adverse events were mostly of grades 1 and 2. Seven of 9 treated patients had a detectable TG1042-derived IFN-gamma message in injected lesions after the first treatment cycle. A TG1042-IFN-gamma message was also detectable after several treatment cycles. We demonstrate the induction of humoral immune response to lymphoma tumor-antigen se70-2 after treatment. Our study shows that intralesional injections of TG1042 are both safe and well tolerated.

journal_name

Blood

journal_title

Blood

authors

Dummer R,Hassel JC,Fellenberg F,Eichmüller S,Maier T,Slos P,Acres B,Bleuzen P,Bataille V,Squiban P,Burg G,Urosevic M

doi

10.1182/blood-2004-01-0360

subject

Has Abstract

pub_date

2004-09-15 00:00:00

pages

1631-8

issue

6

eissn

0006-4971

issn

1528-0020

pii

2004-01-0360

journal_volume

104

pub_type

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