Hybridoma technology was originally improved by Dr. Lee in 1982 and has been refined over the years into a 50-hour methodology for cell fusion and cloning of hybridomas to generate MABs. This improved technology has enabled VBL to generate high quality MABs which have been commercialized and licensed to several major diagnostic companies.
The most distinguished MAB is Anti-human Cardiac Troponin I (TPC110), which is the premier biomarker for diagnosis of acute myocardial infarction (AMI). It is routinely used in emergency rooms across the world to diagnose AMI and monitor the progression of cardiac injury. The sales of TPC110 have dominated as much as 70% of the US diagnostic market with a production of 60-80 grams per annum.
RP215 was one of the 3,000 MABs generated against ovarian cancer cell extracts in 1987. It was later shown in 2006 to specifically recognize a unique carbohydrate-associated epitope located mainly in the variable regions of immunoglobulin heavy chains which are widely expressed on the surface of almost all human cancer cells (the broad-spectrum cancer-derived antigen CA215).
Since 2005, it has been demonstrated that RP215 can suitably target almost all cancer cells which show high surface expression of immunoglobulins upon interactions. RP215 can induce apoptosis and related immune-cytotoxicity to cancer cells in vitro and in vivo. Therefore, unique anti-cancer drugs or specific therapeutic treatments can be developed to cure human cancer for many tissue origins. Since 1997, several VBL US and European patents have been approved or are pending for the potential clinical applications of RP215.
Recently, chimeric antigen receptor (CAR) T-cell therapy has become a popular choice for cancer treatment. With the advancement of this technology, RP215-related genes can be incorporated into this format. RP215 gene-transfected T-cells can be expanded in vitro and re-introduced to the autologous individual for CAR T-cell therapy to effectively fight against cancer.
VBL recently licensed RP215 to iO Biosciences Inc. (iO BiO) of Philadelphia, USA for a five-year co-development plan. This plan will utilize universal, stem cell-derived, natural killer (NK) cells engineered to express CARs along with iO BiO’s proprietary GEMS technology to advance cancer fighting immunotherapy.
Since CA215 is mainly associated with cancerous immunoglobulins with a unique RP215-specific epitope, it can be regarded as a pan-cancer marker (PCM) for monitoring of various human cancers by immunoassays. Cancer detection rates for various human cancers are greatly improved with a combination of CA215 PCM and other known tissue-oriented cancer markers including AFP, CEA, CA125, CA15-3, CA199, and cyfra-21-1. Additionally, CA215 can also be utilized for cancer monitoring when used in combination with other known PCMs.
GHR106 is another distinct MAB generated against human GnRH receptors, abundantly expressed on the surfaces of almost all human cancer cells. Long-lived (circulation half-life of 5-12 days) GHR106 MABs can be developed and used to induce apoptosis of cancer cells, similar to that of short-lived (circulation half-life of minutes to hours) GnRH analogs.
Therefore, GHR106 MABs can be regarded as first-in-class antibodies for applications in anti-cancer treatment. Similar to the case of RP215, GHR106 related genes can also be incorporated into CAR T-Cell therapy systems. GHR106 is ready for validation and approval via clinical trial studies. GHR106 is also part of the co-development plan with iO BiO.
GHR106 is one of numerous MABs which were generated against N1-29 synthetic peptide corresponding to the extracellular domains of human GnRH receptors. GHR106 can be used as a long-acting, high molecular weight GnRH antagonist. GHR106 has several potential applications in therapeutics including regulating and controlling premenstrual syndrome, endometriosis, spontaneous ovulation in fertility treatment, and other gynaecological diseases. GHR106 for these applications are part of the co-development plan with iO BiO.
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