公开(公告)号：US20250101108A1

公开(公告)日：2025-03-27

申请号：US18709427

申请日：2022-11-16

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Roger S. Lo ,  Zhentao Yang

IPC: C07K16/28 ,  A61K31/18 ,  A61K31/352 ,  A61K31/409 ,  A61K31/4162 ,  A61K31/454 ,  A61K31/519 ,  A61K39/00 ,  A61K45/06 ,  A61P35/00

Abstract: Described are methods for enhancing cancer immune surveillance and the efficacy of the treatment of melanoma or non-melanoma cancers such as pancreatic or colorectal cancers, particularly by controlling cancer cell-surface PD-L1/L2 and the E3 ligase ITCH. Also described are methods of inhibiting an adaptive immune resistance response to anti-immune checkpoint protein therapy in a subject. As described herein, the efficacy of MAPK inhibitor therapy is increased by treatment with an activator of E3 ligase ITCH or a destabilizer of cell-surface PD-L1/L2. As further demonstrated herein, the efficacy of anti-PD-1/L1 therapy is also increased by treatment with an activator of E3 ligase ITCH or a destabilizer of cell-surface PD-L1/L2.