Oncolytic adenovirus ICOVIR-7 in patients with advanced and refractory solid tumors.
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.
Nokisalmi
Petri
P
Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Pesonen
Sari
S
Escutenaire
Sophie
S
Särkioja
Merja
M
Raki
Mari
M
Cerullo
Vincenzo
V
Laasonen
Leena
L
Alemany
Ramon
R
Rojas
Juan
J
Cascallo
Manel
M
Guse
Kilian
K
Rajecki
Maria
M
Kangasniemi
Lotta
L
Haavisto
Elina
E
Karioja-Kallio
Aila
A
Hannuksela
Päivi
P
Oksanen
Minna
M
Kanerva
Anna
A
Joensuu
Timo
T
Ahtiainen
Laura
L
Hemminki
Akseli
A
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
D000914:Antibodies, Viral; D007378:Interleukins