Title : Antibody-proteases as translational tools of the next-step generation to be applied for biotech, bioindustry and personalized and precision medical practice
Abstract:
Antibodies (Abs) against myelin basic protein/MBP endowing with proteolytic activity (Ab-proteases with functionality) are of great value to monitor demyelination to illustrate the evolution of multiple sclerosis (MS). Along with canonical Abs, some of the families proven to occur are Abs possessing with catalytic activity (abzymes), and thus to belong to Abs with functionality! Abs against myelin basic protein/MBP endowing with proteolytic activity (Ab-proteases with functionality) are of great value to monitor demyelination to illustrate the evolution of MS. Catalytic Abs are immunoglobulins (Igs) endowed with enzymatic properties. The activity of Ab-proteases in combination with the sequence-specificity would confirm a high subclinical and predictive (translational) value of the tools as applicable for personalized monitoring protocols. Sequence-specific Ab-proteases have proved to be greatly informative and thus valuable biomarkers to monitor MS at both subclinical and clinical stages! And the translational potential of this knowledge is in the rational design of new diagnostic tools and new therapeutics based on principles of artificial biocatalysts. Meanwhile, the drastic improvements in design-inspired and biotech-driven engineering technologies, combined with the innovations in trans-disciplinary sciences, suggesting that catalytic Abs have opened the way to new translational applications for these combinatorial tools. Ab proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally new catalysts with no natural counterparts. Therefore, the proposed predictive value of MBP-targeted Ab-proteases for the development of MS is being challenged and could be utilized in developing diagnostic tools of the next step generation. Meanwhile, proteolytic Abs made it feasible to develop new catalysts, which had previously been the subject of translational research. And such Abs can thus continue to play a role and even fully prevent the emergence of autoimmune disorders, especially in the field of infection and immunity, where the process of its occurrence and development often takes a long time. The exquisite specificity, natural biological functions, and favorable development properties of proteolytic Abs make them highly effective agents as drugs. Enzymes (as part of catalytic Abs) are able to catalytically turnover multiple substrates, making them a natural sub-stoichiometric solution for targets of high abundance or in poorly accessible sites of action. However, enzymes have their own limitations as drugs, including, in particular, the polypharmacology and broad specificity often seen with native enzymes. In this context, we might suggest and thus introduce Ab-guided proteolytic enzymes to enable selective sub-stoichiometric turnover of therapeutic (possibly, preventive, prophylactic and rehabilitative in the future to come) targets. The catalytic Abs paired with Ab-mediated substrate targeting can enhance enzyme activity and specificity, with proof of concept for the challenging target proteins. The experts in the field would have to become open to advanceand develop a design-driven innovative biotherapeutic platform to get the favorable properties of Abs and proteolytic enzymes integrated to effectively prompt the future of the therapeutic efficacy of the designed medicine. New possibilities arise for their therapeutic applications. Ab-directed abzyme prodrug therapy (ADAPT) might largely replace Ab-directed enzyme prodrug therapy (ADEPT) for selective and/or targeted delivering some agents th the affected tissues. Of tremendous value in this sense are Ab-proteases directly affecting the physiologic remodeling of tissues with multilevel architectonics (for instance, myelin)., whilst securing the requests and standards of regeneration and remyelination. They can enzymatically cleave specific surface proteins on viruses or tumor cells, thereby disrupting the invaders. Rationales are being accumulated and integrated for the requirements of catalytic Abs with regard to drug dependence in humans and their eventual realization as clinical therapeutics. The latter means that further studies on Ab-mediated MBP degradation and other targeted Ab-mediated proteolysis may provide biomarkers of newer generations and thus a supplementary tool for assessing the disease progression and predicting disability of the patients and persons-at-risks.
