title: The first clinical use of a live-attenuated Listeria monocytogenes vaccine: a Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix.
abstract: Invasive carcinoma of the cervix (ICC) is the second most common cancer in women worldwide. Lm-LLO-E7 vaccine is a live-attenuated Listeria monocytogenes (Lm) that secretes the HPV-16 E7 antigen fused to a non-hemolytic fragment of the Lm protein listeriolysin O (LLO). In this Phase I trial, the safety of Lm-LLO-E7 was assessed in 15 patients with previously treated metastatic, refractory or recurrent ICC. Patients received 1 of 3 dose levels of Lm-LLO-E7 (1 x 10(9)CFU, 3.3 x 10(9)CFU or 1 x 10(10)CFU) as an intravenous infusion, followed by a second dose 3 weeks later. All patients experienced a flu-like syndrome which responded to non-prescription symptomatic treatment. Severe (grade 3) adverse events related to Lm-LLO-E7 were reported in 6 patients (40%), but no grade 4 adverse events were observed. At the highest dose some patients had severe fever and dose limiting hypotension. By the end of the study protocol, 2 patients had died, 5 had progressed, 7 had stable disease and 1 qualified as a partial responder. This study shows for the first time that a live-attenuated Lm is safe to be administered to late stage ICC patients.
authors.affiliation: Advaxis Inc 675 US 1 North, North Brunswick, NJ 08902, USA. maciag@advaxis.com
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Maciag
authors.forename: Sinisa
authors.initials: S
authors.lastname: Radulovic
authors.forename: John
authors.initials: J
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology
chemical_list: D053918:Papillomavirus Vaccines; D014613:Vaccines, Attenuated