Phase I Trial of Intraperitoneal Administration of an Oncolytic Measles Virus Strain Engineered to Express Carcinoembryonic Antigen for Recurrent Ovarian Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 3; pp. 875 - 882
• Main Authors: GALANIS, Evanthia, HARTMANN, Lynn C, SLOAN, Jeff A, KEENEY, Gary, ATHERTON, Pamela J, PODRATZ, Karl C, DOWDY, Sean C, STANHOPE, C. Robert, WILSON, Timothy O, FEDERSPIEL, Mark J, PENG, Kah-Whye, RUSSELL, Stephen J, CLIBY, William A, LONG, Harry J, PEETHAMBARAM, Prema P, BARRETTE, Brigitte A, KAUR, Judith S, HALUSKA, Paul J, ADERCA, Ileana, ZMAN, Paula J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-2010
• Subjects: Abdominal Pain - etiology; Adult; Aged; Aged, 80 and over; Animals; Antineoplastic agents; Biological and medical sciences; Carcinoembryonic Antigen - genetics; Carcinoembryonic Antigen - metabolism; Cercopithecus aethiops; Fatigue - etiology; Female; Female genital diseases; Fever - etiology; Gynecology. Andrology. Obstetrics; Humans; Injections, Intraperitoneal; Measles virus - genetics; Measles virus - physiology; Medical sciences; Middle Aged; Neoplasm Recurrence, Local; Oncolytic Virotherapy - adverse effects; Oncolytic Virotherapy - methods; Oncolytic Viruses - genetics; Oncolytic Viruses - physiology; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Pharmacology. Drug treatments; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - adverse effects; Treatment Outcome; Tumors; Vero Cells; Human; Relapse; Intraperitoneal administration; Tumor associated antigen; Oncofetal antigen; Ovary cancer; Tumoral marker; Malignant tumor; Oncolytic virus; Gene expression; Paramyxoviridae; Female genital diseases; Strain; Virus; Paramyxovirinae; Ovarian diseases; Carcinoembryonic antigen; Mononegavirales; Morbillivirus; Phase I trial; Cancer; Measles virus
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-2762

Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (10(3)-10(9) TCID(50)). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54-277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3-38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients.