Phase II Trial of a Single Weekly Intravenous Dose of Ranpirnase in Patients With Unresectable Malignant Mesothelioma

Abstract

Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.

Ranpirnase (Frog RNase) Targeted with a Humanized, Internalizing, Anti–Trop-2 Antibody Has Potent Cytotoxicity against Diverse Epithelial Cancer Cells

“…We expect to gain an initial insight into the potential immunogenicity of (Q)-hRS7 with future studies in Cynomolgus monkeys, which may also reveal whether there is an antigen sink for hRS7. However, we believe that (Q)-hRS7 should be less immunogenic because it comprises the fusion of a humanized antibody to a toxin that seems to induce little antibody response in patients (6).…”

“…The extensively studied Rap (4) has recently completed a randomized phase IIIb clinical trial, which compared the effectiveness of Rap plus doxorubicin with that of doxorubicin alone in patients with unresectable malignant mesothelioma, with the interim analysis showing that the MST for the combination was 12 months, whereas that of the monotherapy was 10 months (5). Rap can be administered repeatedly to patients without any untoward immune response, with reversible renal toxicity reported to be dose limiting (6,7).…”

Cytotoxic Ribonucleases and RNA Interference (RNAi)

“…[5][6][7][8][9][10] Onc is cytostatic and cytotoxic to tumor cell lines of different lineage, [11][12][13][14][15] inhibits tumor growth in mice, 16,17 and under the trade name of ONCONASE® its antitumor properties are being currently evaluated in Phase III clinical trials. 18 The mechanism by which Onc exerts cytostatic and cytotoxic activity is not well understood. Onc binds to the receptors on cell surface with two different affinities (Kd = 6.2 x 10 -8 and 2.5 x 10 -7 ), 14,16 is internalized into the cell by a dynamin-independent endocytic pathway 19,20 where it inhibits protein synthesis.…”

X-ray Structure of Two Crystalline Forms of aStreptomycete Ribonuclease with Cytotoxic Activity

“…The cytotoxic activity of some vertebrate ribonucleases has led to their development as cancer chemotherapeutics (42)(43)(44). For example, onconase, which is the homolog of RNase A in the Northern leopard frog (Rana pipiens), is now in Phase III clinical trials for the treatment of malignant mesothelioma, a form of lung cancer (45). A few fungal ribonucleases are also known to have antitumor activity (46).…”