Abstract

Monoclonal Antibody and Drug combination Therapy for an Effective Treatment of Type I Diabetes

T Mahesh, Research Scholar, JSS College of Pharmacy

Antibodies are an important, naturally occurring part of the immune system, large molecules that can specifically bind to the cell surface of an “encroacher” in to the system. Type 1 diabetes mellitus (T1DM) is believed to be due to the autoimmune destruction of ß-cells by T lymphocytes; however, there is growing evidence that B lymphocytes play a role in many T-lymphocyte–mediated diseases. Many T-lymphocyte mediated diseases include B-lymphocytes Component It is possible to achieve selective depletion of these B lymphocytes with, an Anti-CD20 monoclonal antibody. Antibody-drug conjugates (ADCs) represent an exciting and promising therapeutic approach in present research. ADC’s concept is a less explored and more trustable for the treatment of T1DM.This concept has led to initiate the use of anti-CD20 mAb against B-lympocytes which are involved in T-cell mediated diseases by transient eliminating of B lymphocytes with rituximab would decrease immune-mediated destruction of beta cells and result in preserving beta-cell function and C-peptide loss in type 1 diabetes of recent onset. Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates ß-cells proliferation. The half life of GLP-1 hormone is less due to rapid degradation by DPP-IV enzyme, so an alternative DPP-IV-inhibitors can increase the half life of GLP-1 through which it conquers the replacement and reserve ß-cells mass. Thus in the present study Anti-CD20 mAb which can act as a path finder is conjugated with Sitagliptin a payload, which is a DPP-IV inhibitor. Anti-CD20 antibody mAb was conjugated with sitagliptin(SP) Nano particle (NP) SP-NPs via twostep process involving the thiolation of free carboxyl groups on the NPs surface, followed by the covalent attachment of anti-CD20 monoclonal antibodies to thiolated NPs via a sulfo-MBS cross-linker. The conjugation of Anti-CD20 mAb with SP-NPs was confirmed Qualitatively by Transmission Electron Microscope (TEM) and quantitatively by HPLC method which showed substantial results. Hence this combination therapy could be an alternative approach for diabetes treatment.