Phase II Clinical Trial of Intratumoral Application of TG1042 (Adenovirus-interferon-γ) in Patients With Advanced Cutaneous T-cell Lymphomas and Multilesional Cutaneous B-cell Lymphomas

Abstract

Cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative disorders that are manageable by immunotherapy. Twenty-one patients were enrolled in a prospective open-label, dose-escalation multicenter study evaluating the effects of repeated TG1042 [adenovirus-interferon (IFN)-gamma] intralesional injections in patients with primary CLs, of which 18 were of T-cell and 3 of B-cell type. Repeated intralesional therapy using TG1042 consistently results in local tumor regressions in about half of treated patients and one-third of patients also in regressions in noninjected distant lesions, likely reflecting the systemic immune activation after intralesional therapy. Treatment was well tolerated with few adverse events including injection site reactions, chills, lymphopenia, and fever. Immune monitoring in the peripheral blood demonstrated systemic immune activation and the induction of antibodies against tumor antigens in some patients without clear association with clinical responses. CLs, in particular B-cell lymphomas with high objective response rates, seem to be excellent targets for this type of immunotherapy.

Surgical immune interventions for solid malignancies

“…(11, 51–57) Of these, adenoviral-vector delivery of interferon-gamma has shown significant response rates, with local tumor regression in 8 out of 15 patients with cutaneous lymphomas. (56) Additionally, this trial demonstrated systemic responses in 4 out of 15 patients, which highlights systemic distribution despite a regional intratumoral injection. Intratumoral oncolytic viral therapies have been evaluated in pancreatic and hepatocellular cancers with some increases in lymphocyte infiltration.…”

In Situ Vaccination with Adenoviral Vectors to Treat Cancer

“…20,21,24,[26][27][28][29][30][39][40][41][42][43][44][45][46][47] We also noted that although intrapleural gene transfer was detectable, we saw it at the surface of the pleural tumors. We did not reach a maximally tolerated dose.…”

Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma

“…Considerable experimental data from our group and other investigators demonstrated that intratumoral IFN-γ gene transfer to achieve long-term, continuous locoregional exposure of IFN-γ is likely an appropriate approach for improving efficacy and reducing toxicity of IFN-γ [9,10,15,16,23,24]. In this study, we reported that adenovirus-mediated IFN-γ gene transfer (Ad-IFNγ) inhibited tumor growth of human nasopharyngeal carcinoma (NPC) cells (Figure 2 and Figure 5).…”

“…However, the clinical application of recombinant IFN-γ protein is hampered by its short half-life and significant side effects. IFN-γ Gene therapy can continuously produce and release therapeutic protein in local focus to overcome the obstacle of recombinant IFN-γ protein [9,10,15,16]. …”