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

Inventors

Romero, Augustin T. • QIN, Bolin

Assignees

Gts Biotech LLC

Abstract

Processes for 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 disclosure describes processes and compositions using Type-A polymers consisting of A-type singly and/or doubly linked procyanidin oligomers of catechins and/or epicatechins, including cinnamtannin D-1 and/or cinnamtannin B-1. The disclosed compositions modulate PD-1/PD-L1 pathway gene and protein expression by decreasing CD274 (PD-L1) and increasing PDCD1 (PD-1).

The disclosure provides an experimental basis for immunomodulation, including concentration-dependent effects in THP-1 macrophage-like cells and C6 glioma cells measured by immunofluorescence. The disclosed results include PDCD1 upregulation and PD-L1 inhibition, and reversal of LPS- and TNF-α-induced effects in the tested systems.

The disclosure addresses a problem associated with PD-L1 blockade therapies, where cardiac side effects such as cardiomyopathy and heart failure are described. The disclosure positions Type-A polymers and related isolated cinnamtannins as agents to modulate the PD-1/PD-L1 pathway with an aim of improving cardiac tolerability while addressing disease context involving glioma.

Claims Coverage

The independent claim set includes 1 independent claim directed to treating glioma in a human by administering a composition containing isolated cinnamtannin D-1 and isolated cinnamtannin B-1, or a combination. The independent claim requires specified composition content of at least 5.0 weight % of each isolated cinnamtannin where used.

Across the provided material, the central claimed inventive concept is glioma treatment through administration of a composition containing isolated cinnamtannin D-1 and/or isolated cinnamtannin B-1 in defined weight-percent amounts.

Stated Advantages

Documented Applications