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Cell localization features and combination therapy

A technology of therapy and composition, applied in the field of cell localization characteristics and combination therapy, can solve problems such as the complex response of the immune system

Pending Publication Date: 2022-03-11
BRISTOL MYERS SQUIBB CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Immune system and response to immunotherapy have been shown to be complex

Method used

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  • Cell localization features and combination therapy
  • Cell localization features and combination therapy
  • Cell localization features and combination therapy

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Experimental program
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Effect test

Embodiment 1

[0253] Inflammation in the tumor microenvironment (TME), marked by CD8+ T cell infiltration, is associated with improved clinical outcomes across multiple tumor types. Parenchymal infiltration of CD8+ T cells was associated with improved survival with immuno-oncology (I-O) therapy, and intratumoral localization also influenced outcome, highlighting the importance of spatial analysis of CD8+ T cells within the TME. CD8+ T cell patterns within tumors as assessed by immunohistochemistry (IHC) are variable and can be classified as: (i) immune desert (minimal T cell infiltration); (ii) immune exclusion (T cell restricted to tumor stroma or invasive margin); or (iii) immune inflammation (T cell infiltration of tumor parenchyma, located near tumor cells).

[0254] Emerging data demonstrate that artificial intelligence (AI)-based image analysis can be used to characterize tumor parenchyma and stromal compartments in the TME. Pathology data can be quantified, and IHC assays are useful...

Embodiment 2

[0274] In patients with urothelial cancer (UC), gene expression signatures of CD8+ T cell infiltration (CD8 signature, CD8 topography signature) were compared with CD8 IHC using EMT gene expression (CD8.IHC_EMT) vs. Association of volumab response.

[0275] method

[0276] patient

[0277] In a clinical trial (NCT02387996), patients with platinum-pretreated metastatic UC received nivolumab and objective response (OR) was assessed by blinded independent central review.

[0278]In evaluable baseline samples, CD8 IHC was performed by Mosaic Laboratories (Lake Forest, CA) using monoclonal anti-CD8 (C8 / 144B); CD8+ T cell infiltration in parenchymal and interstitial regions was quantified, and tumors were Defined as immune desert, immune exclusion, or immune inflammation phenotype (Fig. 4A-Fig. 4C). EMT gene expression was measured using the HTG EdgeSeq biomarker panel (HTG Molecular Diagnostics, Tucson, AZ), and the EMT signature score was calculated by the arithmetic mean of E...

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PUM

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Abstract

The present disclosure provides a method of identifying a subject suitable for immunooncology (I-O) therapy, the method comprising measuring the expression of one or more of STAT1, IFN [gamma], NECTIN2, and CSF1R. In some aspects, the I-O therapy comprises administering to the subject an anti-PD-1 antibody, or an antigen-binding portion thereof, or an anti-PD-L1 antibody, or an antigen-binding portion thereof.

Description

[0001] Cross References to Related Applications [0002] This PCT application claims the benefit of priority to U.S. Provisional Application No. 62 / 854,887, filed May 30, 2019, and U.S. Provisional Application No. 62 / 931,725, filed November 6, 2019, each of which is incorporated by reference in its entirety This article. technical field [0003] The present disclosure provides a method for treating a subject with a tumor using immunotherapy. Background technique [0004] Human cancers have numerous genetic and epigenetic alterations that generate neoantigens that are potentially recognized by the immune system (Sjoblom et al., Science (2006) 314(5797):268-274). The adaptive immune system, composed of T and B lymphocytes, has a powerful anticancer potential, with broad capabilities and precise specificity in response to diverse tumor antigens. Furthermore, the immune system exhibits considerable plasticity and memory components. Successfully harnessing all of these propert...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574A61K39/395A61P35/00
CPCC12Q1/6886G01N33/57484C07K16/2818C07K16/2827C07K16/2866A61P35/00C12Q2600/106C12Q2600/158G01N2800/52A61K2039/505A61K2039/507G01N33/574A61P35/04A61K39/3955A61K45/06C12Q1/6869G01N33/57492
Inventor P·萨伯张兰K·H·德赛N·阿德亚戚振豪A·格林菲尔德G·C·李S·A·伊利S·潘特G·A·格林
Owner BRISTOL MYERS SQUIBB CO
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