Inhibited expression of PD-L1 and enhanced expression of PD-1

Inventors

Romero, Augustin T. • QIN, Bolin

Assignees

Gts Biotech LLC

Abstract

Processes for treating an autoimmune disease or condition by decreasing expression of a CD274 gene and/or a PD-L1 protein and increasing expression of a PDCD1 gene and/or a PD-1 protein in a subject in need of such expression changes are provided. The processes include administering to the subject a composition including at least 0.5% of cinnamtannin D-1 and/or cinnamtannin B-1. The processes further include decreasing expression of a CD274 gene and/or a PD-L1 protein and increasing expression of a PDCD1 gene and/or a PD-1 protein in the subject by the step of administering at the desired concentration or for the desired time wherein the composition may increase or decrease the relative expression levels of the genes or proteins while simultaneously ameliorating, preventing, or modulating a cardiac event in the subject.

Core Innovation

The invention relates to treating a human suffering from an autoimmune dilated cardiomyopathy, autoimmune encephalomyelitis, or rheumatoid arthritis by modulating the PD-1/PD-L1 checkpoint. The disclosed approach administers Type-A polymers that include A-type singly and doubly linked procyanidin oligomers of catechins and/or epicatechins, including cinnamtannin D-1 and/or cinnamtannin B-1. The treatment is associated with decreasing CD274 (PD-L1) and/or PD-L1 protein while increasing PDCD1 (PD-1) and/or PD-1 protein.

The disclosed Type-A polymers are described as A-type linked procyanidin oligomers, and the document specifies polymer characterization including A-type linkages and typical oligomer masses. The composition includes cinnamtannin D-1 and/or cinnamtannin B-1 at weight percent levels, and biological results are reported for modulation of PDCD1/PD-1 and PD-L1/PDCD1 response.

Biological characterization includes immunofluorescence and densitometry in THP-1 and C6 glioma models showing increased PDCD1/PD-1 expression and decreased PD-L1/PDCD1 response under stimuli including LPS and TNF-α. Quantitative percent changes across concentrations are reported, supporting the checkpoint modulation concept for the stated autoimmune conditions.

Claims Coverage

The partial claim set includes one independent claim covering a treating process for each of autoimmune dilated cardiomyopathy, autoimmune encephalomyelitis, and rheumatoid arthritis, using compositions with isolated cinnamtannin D-1 and/or isolated cinnamtannin B-1 at specified minimum weight percentages. Dependent claims refine composition and administration parameters, including dosage amount constraints, active ingredient scope, administration routes, treatment duration, and optional additional vitamins and/or antioxidants.

Across the independent and dependent claims provided, the inventive coverage centers on effectively treating autoimmune dilated cardiomyopathy, autoimmune encephalomyelitis, and/or rheumatoid arthritis through administration of a composition containing isolated cinnamtannin D-1 and/or isolated cinnamtannin B-1 at specified weight percent levels, with further refinements to amount, active-ingredient scope, delivery routes, duration, and optional added vitamins and/or antioxidants.

Stated Advantages

Documented Applications