Celgene Corporation

Bristol-myers Squibb Compnay

Anke Klippel

Kyle MacBeth

Rajesh Chopra

Anita Gandhi

Courtney G Havens

Patrick Hagner

Paul Hollenbach

Suzana Sturlini Couto

Matthew William Burnell Trotter

Maria Yinglin Wang

Mike Breider

Yan Ren

Laurence Celine Menard

Matthew William Trotter

Provided are transgenic mice whose genome comprises a nucleic acid sequence encoding human cereblon (CRBN) or a fragment thereof, wherein endogenous mouse CRBN is not expressed in the transgenic mice. Also provided are cells, cell lines, tissues, and organs derivable from the transgenic mice, and methods for producing and using such mice.

Transgenic mouse expressing human cereblon

Provided herein are methods for treating a subject afflicted with a cancer, comprising administering to the subject a TIM3 agonist (e.g., an anti-TIM3 antibody), alone or in conjunction with another immune checkpoint inhibitor (e.g., a PD-1 antagonist), wherein the subject is identified as having a high frequency of TIM3 positive cells (e.g., on the tumor infiltrating inflammatory cells) or soluble TIM3 in peripheral blood. Also provided are methods for assessing the efficacy of a treatment comprising a TIM3 antagonist in a subject afflicted with a cancer, comprising measuring the frequency of TIM3 (and optionally PD-1) positive cells in certain populations of cells and/or the soluble TIM3 in peripheral blood of the subject, wherein a high frequency of TIM3 (and optionally PD-1) positive cells and/or the subject's peripheral blood titer of soluble TIM3 is indicative of the response to the treatment.

TIM-3 antagonists for the treatment and diagnosis of cancers

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.

Methods for determining drug efficacy for the treatment of diffuse large B-cell lymphoma, multiple myeloma, and myeloid cancers

Growing community of inventors

Westfield, NJ, United States of America

Anke Klippel