Cancer metastasis is responsible for more than 90% of the cancer deaths worldwide. There is an urgent necessity to find new therapeutic targets to control metastatic spread in colorectal cancer and other tumors. Many unsuccessful attempts have been made in the last decades to target integrins for cancer therapy.
The group of Dr. Ignacio Casal at CIB hypothesized that targeting α2β1 integrin activation with cadherin RGD blocking monoclonal antibodies would be an efficient procedure to reduce metastatic spread in multiple tumors.
In this work, recently published in the Journal of Clinical Cancer Research, the researchers have generated monoclonal antibodies (mAbs) against a 9-mer peptide containing the RGD motif and flanking sequences of cadherin 17. They demonstrated that cellular cadherin RGD motifs are highly efficient and function as selective targets for α2β1 integrin inhibition in metastatic cells. Moreover, they describe the functional characterization of cadherin RGD-specific monoclonal antibodies, which have demonstrated an extraordinary efficiency in blocking β1 integrin activation and protecting mice against liver and lung metastasis from human colorectal cancer and melanoma cells, respectively.
All the collected data support that these highly promising results can be also extended to breast, pancreatic and other malignant tumors. In summary, these highly selective monoclonal antibodies open a new avenue for the treatment of metastasis in different types of human cancer.
Due to this promising data, a patent has been licensed on these monoclonal antibodies in collaboration with the company Protein Alternatives S.L.
Reference: Monoclonal antibodies directed against cadherin RGD exhibit therapeutic activity against melanoma and colorectal cancer metastasis. Rubén A. Bartolomé, Carmen Aizpurua, Marta Jaén, Sofía Torres, Eva Calviño, Juan I. Imbaud and J. Ignacio Casal. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-17-1444
CSIC Press Release (in spanish)
RTVE news (September 29th), from minute 40 (in Spanish)