公开(公告)号：US10744116B2

公开(公告)日：2020-08-18

申请号：US16084911

申请日：2017-03-16

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Roger S. Lo ,  Willy Hugo ,  Antoni Ribas ,  Jesse Zaretsky

IPC: G01N31/00 ,  A61K31/385 ,  C12Q1/6886 ,  C07K16/28 ,  G16B20/00 ,  A61P35/00 ,  G16B5/00 ,  G16B25/00 ,  A61K31/337 ,  A61K31/427 ,  A61K39/395 ,  A61K45/06 ,  C12Q1/686 ,  G16B25/10

Abstract: Methods of predicting or detecting sensitivity to therapeutic effects of anti-PD-1 therapy in a patient suffering from melanoma, as well as for selecting somatic mutanomes and transcriptomes of melanoma biopsies. A tumor sample obtained from the patient is assayed for a measure of anti-PD-1 therapy sensitivity via, for example, whole transcriptome sequencing, antibody based protein quantifications, mass spectrometry based protein quantification, targeted mRNA sequencing, real-time RT-PCR, Sanger sequencing, targeted sequencing and/or whole exome/genome sequencing. Samples are selected that exhibit a higher first enrichment similarity score and/or a lower second enrichment similarity score, and/or at least one measure of sensitivity. A patient whose sample was selected herein as a candidate for anti-PD-1 therapy is thereby identified. The method of the invention can further comprise treating the patient with anti-PD-1 therapy, optionally in conjunction with combinatorial therapy.

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.

公开(公告)号：US20240393339A1

公开(公告)日：2024-11-28

申请号：US18694670

申请日：2022-09-23

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Roger S. Lo

IPC: G01N33/574 ,  A61K45/06 ,  A61P35/00 ,  C07K16/28

Abstract: Methods of treating resectable head and neck cancer based on analyses of blood and tumor samples collected over the course of a clinical trial and during follow-up after the clinical trial. Omic or multi-plex molecular tools were used to analyze the tissues and identify objective molecular markers and pathogenic mechanisms associated with favorable or unfavorable outcomes. These analyses form the basis for a treatment strategy that improves outcomes by tailoring the treatment to the molecular features of individual patients' blood samples and tumors. This method for personalized treatment distinguishes between subjects who respond to neoadjuvant anti-PD-1/L1 therapy and patients who do not respond to such neoadjuvant therapy, so that treatment is tailored to the subject's responder profile. This approach avoids exposing patients to unnecessary toxicity, and avoids delaying surgical resection when no advantage will be gained by delaying surgery to allow for neoadjuvant therapy.

公开(公告)号：US20250066480A1

公开(公告)日：2025-02-27

申请号：US18294767

申请日：2022-08-01

Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Roger S. Lo

IPC: C07K16/28 ,  A61K38/17 ,  A61K39/00 ,  A61P35/04

Abstract: A method of enhancing efficacy of mitogen-activated protein kinase inhibitor (MAPKi) therapy or immune checkpoint therapy (ICT), as well as a method of suppressing melanoma brain metastasis in a subject, and a method of inhibiting intratumoral M2-like tumor associated macrophages (TAMs) or regulatory T cells (TREG) in a subject comprises (a) pretreating a subject appropriate for and in need of MAPKi therapy by administering one or more doses of ICT to the subject; and (b) subsequent to the pretreating of (a), administering to the subject a combination of MAPKi and ICT. The ICT typically comprises an anti-PD-1 or anti-PD-L1 agent. Optionally, the ICT further comprises additional agents (such as anti-CTLA4 and/or anti-LAG3) to enhance the efficacy of MAPKi therapy.