NTI’s present patented technology is based on protocol development and antigen availability prerequisite to creating antibody arrays with potential for early organ site-specific detection of cancer based on serum presence of cancer specific tNOX isoforms. The tNOX isoforms result from the cancer-specific expression of splice variant mRNAs derived from a single gene. The final outcome anticipated is a simple, rapid and inexpensive monoclonal antibody designed for early serum detection of all major forms of human cancer. Final array are anticipated to provide quantitation of 20 to 30 cancer organ site-specific NOX isoforms with clinically verified, diagnostic and prognostic indications.
NTI technology fills a thus-far unmet need for single biomarkers and combinations of biomarkers generally accepted as having the sensitivity and specificity required to diagnose early-stage cancer. Our technology provides an array of tNOX isoforms that are cancer and organ site-specific potentially amenable to detection by innovative technologies, from a limited amount of sample (20 &mu l or less of serum or urine) with a very low incidence of false positives and with detection at the earliest possible stages and well before cancer spread.
See Isoforms
Thus far, we have identified characteristic tNOX isoforms unique to the major forms of epithelial cancers including small cell lung, breast, ovarian, colon, cervical, pancreas and prostate. Additionally, we have isoforms characteristic of melanoma and hematological cancers. In total, we have evidence from 2-D gel electrophoresis for approximately 25 different tNOX isoforms which are both cancer-specific and, generally, organ site-specific. All are absent or below the limits of detection with sera from individuals not diagnosed with cancer or diagnosed with diseases other than cancer. We plan to rapidly expand the list to bring the total tNOX isoform inventory to between 30 and 40 including those characterizing different hematological cancers. Currently, tNOX-specific antigens are available from each of the isoforms already characterized and the remainder will become available as they are discovered and characterized. Antibody production to three of the antigens non small-cell lung, breast and ovarian is underway and all three tNOX isoform sources appear to be sufficiently antigenic to support isoform-specific monoclonal antibody generation.
Early detection remains a critical need in cancer management. Detection of cancer in early stages increases the availability of treatment options, which greatly improves chances of survival. Availability of a new class of circulating serum biomarkers for cancer would greatly facilitate both research (i.e., non-invasive monitoring for cancer presence in prevention trials) and for therapy (initiation of therapeutic intervention at the earliest possible stages). The proposed test would be non-invasive (routine blood draw), inexpensive and rapid.
Cancer-specific tNOX isoform patterns from patient sera for early detection are both new and unique. Utility has been demonstrated in laboratory studies with sera of cancer patients, yet clinical utility is thus far restricted to preliminary but promising studies. The use of tNOX isoform patterns to predict therapeutic response or to provide guidance to clinical management is also conceptually new.
The tNOX isoforms thus far appear to be cancer-specific and are undetectably low or absent in sera of patients without cancer. Unlike most published cancer markers, this method does not simply measure elevated levels of a serum constituent present in lesser amount in the absence of cancer. Neither the splice variant mRNAs nor the tNOX isoform proteins are present in detectable levels in non-cancer cells (See MORE ABOUT tNOX).