In 1998, we identified PRL3 gene (Zeng et al., BBRC 1998). In 2001, Professor Vogelstein and his team from Johns Hopkins University first demonstrated a role of PRL3 gene in cancer progression and metastasis (Saha et al., Science 2001).
PRL3 is an intracellular protein (inside cell) overexpressed in many tumors and has been reported globally by many research laboratories. Since PRL3 is specifically overexpressed in tumors but undetectable in most normal tissues, we anticipate that PRL3 is an excellent tumor specific antigen for cancer therapy. Traditionally, intracellular oncoproteins (such as PRL3) are targeted by small chemical inhibitors (chemotherapy), mainly because intracellular compartments are presumed to be inaccessible to large antibody drugs. However, as compared to chemotherapy, antibody therapy is more target specific thus causing less off target side effects.
Our team has dedicated decades of translational research in multiple acute cancer mouse models to develop a new concept of using PRL3 antibody (instead of small chemical inhibitors) to target intracellular PRL3 protein as a novel cancer immunotherapy. Professor Soldano Ferrone, a well-known immunologist from Harvard Medical School described our concept findings (Guo et al., Science Translational Medicine, 2011) as ‘Hidden Immunotherapy Targets Challenge Dogma’ (Perspective STM, 2011).
Recently, we demonstrated that the intracellular PRL3 could be flipped ‘inside-out’ or externalized in the tumor micro-environment and to be bound by PRL3-zumab , which then recruits the immune cells to tumor site, leading to tumor cell death. We revealed the scientific molecular mechanism of action (MOA) model as shown on the left (Thura et al., Nature Communications 2019).
PRL3 oncotarget is overexpressed in > 80 % of tumors across 11 common cancer types that we have examined namely, Acute Myeloid Leukemia (AML), Lung, Liver, Pancreas, Thyroid, Gastric, Kidney, Bladders, Breast, Colon and Prostate. Furthermore, PRL3 oncoprotein has also been reported to be overexpressed in other cancer types, such as Cervical, Ovary, Myeloma, Multiple myeloma, Lymphoma, and many more.
Since PRL3 is a highly tumor-specific target, we therefore generated PRL3-zumab , the First-in-Class humanized antibody as a ‘Research Product’ to move into First in Man in 2017. PRL3-zumab specifically targets PRL3 overexpressing tumors and will not damage surrounding healthy tissues because they do not express the PRL3 oncotarget and this is an alternative to chemotherapy.
We anticipate that our PRL3-zumab is a unique antibody drug to treat multiple cancers overexpressing intracellular PRL3.
Our technology represents an innovative approach of an unconventional cancer immunotherapy against a broad range of cancer types. PRL3-zumab antibody drug will significantly increase therapeutic efficacies and reduce side effects to cancer patients.
