Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5/3-Cox2L-D24 in patients with metastatic and refractory solid tumors.
Eighteen patients with refractory and progressive solid tumors were treated with a single round of triple modified oncolytic adenovirus (Ad5/3-Cox2L-D24). Ad5/3-Cox2L-D24 is the first non-Coxsackie-adenovirus receptor-binding oncolytic adenovirus used in humans. Grades 1-2 flu-like symptoms, fever, and fatigue were seen in most patients, whereas transaminitis or thrombocytopenia were seen in some. Non-hematological grades 3-5 side effects were seen in one patient with grade 3 ileus. Treatment resulted in high neutralizing antibody titers within 3 weeks. Virus appeared in serum 2-4 days after treatment in 83% of patients and persisted for up to 5 weeks. One out of five radiologically evaluable patients had partial response (PR), one had minor response (MR), and three had progressive disease (PD). Two patients scored as PD had a decrease in tumor density. Tumor reductions not measurable with Response Evaluation Criteria In Solid Tumors (RECIST) were seen in a further four patients. PR, MR, stable disease, and PD were seen in 12, 23.5, 35, and 29.5% of tumor markers analyzed, respectively (N=17). Ad5/3-Cox2L-D24 appears safe for treatment of cancer in humans and extended virus circulation results from a single treatment. Objective evidence of anti-tumor activity was seen in 11/18 (61%) of patients. Clinical trials are needed to extend these findings.
Pesonen
S
S
Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.
Nokisalmi
P
P
Escutenaire
S
S
Särkioja
M
M
Raki
M
M
Cerullo
V
V
Kangasniemi
L
L
Laasonen
L
L
Ribacka
C
C
Guse
K
K
Haavisto
E
E
Oksanen
M
M
Rajecki
M
M
Helminen
A
A
Ristimäki
A
A
Karioja-Kallio
A
A
Karli
E
E
Kantola
T
T
Bauerschmitz
G
G
Kanerva
A
A
Joensuu
T
T
Hemminki
A
A
D000256:Adenoviridae / Q000302:isolation & purification; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
D000914:Antibodies, Viral