We have discovered that Cisplatin Resistance-Related Protein 9 (CRR9)/Cleft Lip and Palate Transmembrane 1-Like (CLPTM1L), which is over-expressed in multiple types of cancer, affects survival and proliferation in tumor cells. Increased expression of this protein in tumors is associated with shorter survival in patients with pancreatic cancer. Survival of cellular stresses including hypoxia, oncogene expression, rapid proliferation, genomic instability, and chemotherapeutic insult is a hallmark of cancer. Without CRR9, tumors cannot survive these limitations by which normal cells abide.
We have developed monoclonal antibodies that inhibit the function of CRR9. Lead antibodies (ESS102) inhibit surface accumulation of the protein, interaction with key binding partners, downstream survival signaling, anchorage-independent growth, and chemotherapeutic resistance in lung and pancreatic tumor cells. Preclinical in vivo models show that anti-CRR9 robustly inhibits the growth of both lung and pancreatic adenocarcinomas. The efficacy of anti-CRR9 correlates with specific epitopes representing important targets in human cancers, particularly those driven by KRas, for which effective targeted therapies have been elusive to date.