PURPOSE: Twenty-one patients with cancer were treated with a single round of oncolytic adenovirus ICOVIR-7. EXPERIMENTAL DESIGN: ICOVIR-7 features an RGD-4C modification of the fiber HI-loop of serotype 5 adenovirus for enhanced entry into tumor cells. Tumor selectivity is mediated by an insulator, a modified E2F promoter, and a Rb-binding site deletion of E1A, whereas replication is optimized with E2F binding hairpins and a Kozak sequence. ICOVIR-7 doses ranged from 2 x 10(10) to 1 x 10(12) viral particles. All patients had advanced and metastatic solid tumors refractory to standard therapies. RESULTS: ICOVIR-7 treatment was well tolerated with mild to moderate fever, fatigue, elevated liver transaminases, chills, and hyponatremia. One patient had grade 3 anemia but no other serious side effects were seen. At baseline, 9 of 21 of patients had neutralizing antibody titers against the ICOVIR-7 capsid. Treatment resulted in neutralizing antibody titer induction within 4 weeks in 16 of 18 patients. No elevations of serum proinflammatory cytokine levels were detected. Viral genomes were detected in the circulation in 18 of 21 of patients after injection and 7 of 15 of the samples were positive 2 to 4 weeks later suggesting viral replication. CONCLUSIONS: Overall, objective evidence of antitumor activity was seen in 9 of 17 evaluable patients. In radiological analyses, 5 of 12 evaluable patients had stabilization or reduction in tumor size. These consisted of one partial response, two minor responses and two cases of stable disease, all occurring in patients who had progressive disease before treatment. In summary, ICOVIR-7 treatment is apparently safe, resulting in anticancer activity, and is therefore promising for further clinical testing. Copyright 2010 AACR.
PURPOSE: Twenty-one patients with cancer were treated with a single round of oncolytic adenovirus ICOVIR-7. EXPERIMENTAL DESIGN:ICOVIR-7 features an RGD-4C modification of the fiber HI-loop of serotype 5 adenovirus for enhanced entry into tumor cells. Tumor selectivity is mediated by an insulator, a modified E2F promoter, and a Rb-binding site deletion of E1A, whereas replication is optimized with E2F binding hairpins and a Kozak sequence. ICOVIR-7 doses ranged from 2 x 10(10) to 1 x 10(12) viral particles. All patients had advanced and metastatic solid tumors refractory to standard therapies. RESULTS:ICOVIR-7 treatment was well tolerated with mild to moderate fever, fatigue, elevated liver transaminases, chills, and hyponatremia. One patient had grade 3 anemia but no other serious side effects were seen. At baseline, 9 of 21 of patients had neutralizing antibody titers against the ICOVIR-7 capsid. Treatment resulted in neutralizing antibody titer induction within 4 weeks in 16 of 18 patients. No elevations of serum proinflammatory cytokine levels were detected. Viral genomes were detected in the circulation in 18 of 21 of patients after injection and 7 of 15 of the samples were positive 2 to 4 weeks later suggesting viral replication. CONCLUSIONS: Overall, objective evidence of antitumor activity was seen in 9 of 17 evaluable patients. In radiological analyses, 5 of 12 evaluable patients had stabilization or reduction in tumor size. These consisted of one partial response, two minor responses and two cases of stable disease, all occurring in patients who had progressive disease before treatment. In summary, ICOVIR-7 treatment is apparently safe, resulting in anticancer activity, and is therefore promising for further clinical testing. Copyright 2010 AACR.
Authors: Simona Bramante; Anniina Koski; Ilkka Liikanen; Lotta Vassilev; Minna Oksanen; Mikko Siurala; Raita Heiskanen; Tiina Hakonen; Timo Joensuu; Anna Kanerva; Sari Pesonen; Akseli Hemminki Journal: Oncoimmunology Date: 2015-08-27 Impact factor: 8.110
Authors: Maria Rajecki; Aki Kangasmäki; Leena Laasonen; Sophie Escutenaire; Tanja Hakkarainen; Jarmo Haukka; Ari Ristimäki; Kalevi Kairemo; Lotta Kangasniemi; Timo Kiljunen; Timo Joensuu; Sari Pesonen; Akseli Hemminki Journal: Mol Ther Date: 2011-04 Impact factor: 11.454
Authors: Vincenzo Cerullo; Iulia Diaconu; Lotta Kangasniemi; Maria Rajecki; Sophie Escutenaire; Anniina Koski; Valentina Romano; Noora Rouvinen; Tamara Tuuminen; Leena Laasonen; Kaarina Partanen; Satu Kauppinen; Timo Joensuu; Minna Oksanen; Sirkka-Liisa Holm; Elina Haavisto; Aila Karioja-Kallio; Anna Kanerva; Sari Pesonen; Petteri T Arstila; Akseli Hemminki Journal: Mol Ther Date: 2011-06-14 Impact factor: 11.454