Soluble IGF-1 Receptor for Cancer and Metastasis Overview:

Transcription

Soluble IGF-1 Receptor for Cancer and Metastasis Overview:
Soluble IGF-1 Receptor for Cancer and
Metastasis
Overview:
McGill University is seeking to outlicense intellectual property relating to soluble IGF-1 receptor for
hepatic metastases. We have produced the full length recombinant extracellular protein domain of the
IGF-1 receptor. The protein was administered parenterally to mice (iv or ip) inoculated with H-59 lung
carcinoma cells. There was a marked reduction in hepatic metastases, and in several animals there
was a complete absence of metastatic lesions. Moreover, sustained levels of soluble IGF-1 receptor
protein are detected in blood indicating that the agent has a good PK profile.
Validation:
Figure 1: Liver metastases in mice after
parenteral administration of soluble IGFIR.
Liver metastases were enumerated 14 days
following the instrasplenic/portal inoculation
of tumor H-59 cells, wherein the number of
metastases per liver is shown.
Differentiation:
Other strategies targeted to IGF-1 rely on MAbs. IGF-1 soluble receptor presents advantages:
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High affinity specificity for IGF-1 and IGF-2 (low reactivity with insulin)
Minimal effects on the IR-insulin axis (hyper- and hypoglycemia seen with Abs).
Ability to inhibit the growth promoting effects of both IGF-1R and IR-A in cells that
express both receptor systems (Abs can only block IGF-1R)
Medical need:
The receptor for the type 1 insulin-like growth factor (IGF-IR) has been identified as a major regulator of
the malignant phenotype and a target for cancer therapy. Reducing circulating IGF-1 and IGF-2 levels
represents a potential approach for the treatment of cancer. The present technology relates to the use
of the “soluble” full length extracellular domain of the IGF-1 receptor (sIGF-1R) as a trap to reduce
circulating IGF-1and IGF-2 for the treatment of cancer and liver metastases. For colorectal cancer
which metastasizes almost exclusively to the liver, there are 100,000 new cases in the US annually and
a 5-year survival rate of approximately 50%. High levels of IGF-1 are also a risk factor for other cancers
including breast, prostate and lung.
Inventors: Brodt Pnina et al.
Profile:
Pnina Brodt Ph.D.
Professor, Departments of Surgery, Medicine & Oncology,
McGill University and the McGill University Health Center
Ph.D., McGill University;
M.Sc., University of Ottawa;
B.Sc., Bar-Ilan University
Research:
Dr. Brodt and her group study the molecular aspects of cancer metastasis. In particular, the roles of cell
adhesion receptors, cytokines and growth factors in the regulation of angiogenesis,
cancer cell invasion and metastasis.
Another area of interest is gene therapy of cancer metastases. Multiple strategies are being developed
for gene therapy of metastases based on the targeting and disruption of IGF-IR synthesis and/or signaling.
The role of the host inflammatory response in liver metastasis; cytokines such as TNF and IL-1 and
vascular endothelial adhesion receptors such as E-selectin, VCAM-1, PECAM-1 and ICAM-1
Michèle Beaulieu
Office of Sponsored Research
McGill University
Tel: 514-398-6874
Email: michele.beaulieu@mcgill.ca
Reference code: ROI 09120
Opportunity: Exclusive license or research collaboration