title: Oncolytic adenovirus ICOVIR-7 in patients with advanced and refractory solid tumors.
abstract: OBJECTIVE
  Twenty-one patients with cancer were treated with a single round of oncolytic adenovirus ICOVIR-7.
  
  
  METHODS
  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.
authors.affiliation: Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Nokisalmi
authors.forename: Sari
authors.initials: S
authors.lastname: Pesonen
authors.forename: Sophie
authors.initials: S
authors.lastname: Escutenaire
authors.forename: Merja
authors.initials: M
authors.lastname: Särkioja
authors.forename: Mari
authors.initials: M
authors.lastname: Raki
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
authors.forename: Leena
authors.initials: L
authors.lastname: Laasonen
authors.forename: Ramon
authors.initials: R
authors.lastname: Alemany
authors.forename: Juan
authors.initials: J
authors.lastname: Rojas
authors.forename: Manel
authors.initials: M
authors.lastname: Cascallo
authors.forename: Kilian
authors.initials: K
authors.lastname: Guse
authors.forename: Maria
authors.initials: M
authors.lastname: Rajecki
authors.forename: Lotta
authors.initials: L
authors.lastname: Kangasniemi
authors.forename: Elina
authors.initials: E
authors.lastname: Haavisto
authors.forename: Aila
authors.initials: A
authors.lastname: Karioja-Kallio
authors.forename: Päivi
authors.initials: P
authors.lastname: Hannuksela
authors.forename: Minna
authors.initials: M
authors.lastname: Oksanen
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.forename: Laura
authors.initials: L
authors.lastname: Ahtiainen
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae; D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis; D002648:Child; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D019233:Retreatment; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D007378:Interleukins