Results of a pilot study involving the use of
an antisense oligodeoxynucleotide directed against the insulin-like growth
factor type I receptor in malignant astrocytomas
Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R,
Iliakis G, Aiken RD
Kimmel Cancer Center, Departments of Neurosurgery, Radiology,
Pathology, Internal Medicine, Radiation Oncology, and Neurology, Thomas
Jefferson University Hospital, Philadelphia, PA 19107, USA.
Purpose. Preclinical animal experiments support the use of an antisense
oligodeoxynucleotide directed against the insulin-like growth factor type I
receptor (IGF-IR/AS ODN) as an effective potential antitumor agent.
a human pilot safety and feasibility study using an IGF-IR/AS ODN strategy in
patients with malignant astrocytoma.
Patients and Methods. Autologous glioma
cells collected at surgery were treated ex vivo with an IGF-IR/AS ODN,
encapsulated in diffusion chambers, reimplanted in the rectus sheath within 24
hours of craniotomy, and retrieved after a 24-hour in situ incubation.
posttreatment assessments included clinical examination, laboratory studies, and
magnetic resonance imaging scans.
Results. Other than deep venous thrombosis
noted in some patients, no other treatment-related side effects were observed.
IGF-IR/AS ODN-treated cells, when retrieved and assessed, were < or = 2%
intact by trypan blue exclusion, and none of the intact cells were viable in
Parallel Western blots disclosed IGF-IR downregulation to
< or = 10% after ex vivo antisense treatment.
At follow-up, clinical and
radiographic improvements were observed in eight of 12 patients, including three
cases of distal recurrence with unexpected spontaneous or postsurgical
regression at either the primary or the distant intracranial site.
Ex vivo IGF-IR/AS ODN treatment of autologous glioma cells induces apoptosis and
a host response in vivo without unusual side effects. Subsequent transient and
sustained radiographic and clinical improvements warrant further clinical
PMID: 11304771 [PubMed - indexed for MEDLINE]