Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Immune modulators in combination with radiation treatment

A technology of immunomodulator and ionizing radiation, applied in the field of 004

Inactive Publication Date: 2019-03-15
VARIAN MEDICAL SYSTEMS
View PDF8 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Immunomodulators are being explored to activate the body's own immune system, but are known to have limitations (such as response rates in patients) as monotherapy

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Immune modulators in combination with radiation treatment
  • Immune modulators in combination with radiation treatment
  • Immune modulators in combination with radiation treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120] Example 1: Identification and use of biomarkers to predict response to radiation therapy.

[0121] A radiosensitivity index based on the expression levels of one or more molecular biomarkers can be used to predict the sensitivity of cancer patients to radiation. Genomic biomarkers and other indicators of the tumor microenvironment can also be used to predict patient response to radiation therapy. In addition, molecular target-based biomarkers such as CD44 and TGFβ can predict tumor response.

[0122] CD44 levels have been shown to predict local tumor recurrence after radiotherapy in patients with non-small cell lung cancer (NSCLC). In the study, 133 patients ( figure 1) (see Kumar, S. et al., "Prognostic Biomarkers in Non-Small Cell Lung Cancer Patients Treated With Radiation Therapy: Locally Advanced Non-Small Cell Lung Cancer," International Journal of Radiation Oncology*Biology*Physics, Vol. 90, No. 5, Supplement, 15 November 2014, pp. S25-S26). Tumor samples we...

Embodiment 2

[0128] Example 2: Combination therapy comprising immunomodulators and radiation can enhance inhibition of tumor growth compared to monotherapy.

[0129] In this study, MC38 colon cancer tumor masses (2 x 2 mm) were transplanted into female B57 / BL6 mice (n=5). Tumors were exposed to gamma radiation (2 Gy) on day 8 post-implantation. Immunomodulators, such as anti-TIM4 antibody, anti-MFG-E8 antibody, and anti-M199 antibody, were also administered to the mice on days 9 and 11 after transplantation. 2 mg / kg antibody was injected into each mouse. Tumor volume was measured along three orthogonal axes (x, V, z) and calculated.

[0130] Image 6 Combination therapy of radiation and anti-TIM4 antibody was shown to result in lower tumor growth compared to radiation therapy alone or anti-TIM4 antibody alone. Furthermore, combination therapy of radiation and anti-M199 antibody also showed reduced tumor growth compared to anti-M199 antibody monotherapy. Similarly, anti-MFG-E8 antibody...

Embodiment 3

[0132] Example 3: TIM-4 and MFGE-8 protein expression levels in human tumor samples

[0133] Materials and methods: Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and stained with antibodies targeting TIM-4 or MFGE-8. Two antigen retrieval methods were used for staining: TIM-4: Target retrieval solution (Dako Company), citrate buffer (pH 6.1), at 97°C for 20 minutes; MFGE-8: Target retrieval solution (Dako Corporation) ), Tris EDTA (pH9.0), at 97°C for 20 minutes. Tissue sections were stained using the Dako Envision Flex Kit. Briefly, endogenous peroxides were blocked for 10 min using peroxidase blocking reagent. For mouse tumor tissue, slides were incubated with peroxidase blocking buffer for 1 hour. Mouse tumor tissue slides were rinsed in wash buffer and incubated with Fc receptor blocker for 30 minutes. Mouse tissue sections were also incubated for 30 minutes using mouse detection reagent (Biocare). Tissue sections were incubated with primary an...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Methods for treating tumors by administering ionizing radiation and an immune modulator to a patient with cancer are disclosed. The methods provide the dual benefits of anti-tumor efficacy plus normaltissue protection when combining immune modulators with ionizing radiation to treat cancer patients. The methods described herein also allow for the classification of patients into groups for receiving optimized radiation treatment in combination with an immune modulator based on patient-specific biomarker signatures.

Description

[0001] Cross References to Related Applications [0002] This application is a non-provisional application of U.S. Provisional Application No. 62 / 351,681, filed June 17, 2016, entitled "IMMUNE MODULATORS IN COMBINATION WITH RADIATION TREATMENT," and requires the U.S. The benefit and priority of Provisional Application No. 62 / 351,681, the contents of which are incorporated herein by reference for all purposes. Background technique [0003] Radiation therapy is a key treatment modality for patients with cancer. Radiation can be delivered to tumors with submillimeter precision while substantially sparing normal tissue, ultimately causing tumor cell killing. However, the ability of tumor cells to evade the cell-killing effects of radiation and / or develop resistance mechanisms may counteract the tumor-cell-killing effects of radiation therapy, potentially limiting the therapeutic efficacy of radiation therapy in treating cancer. In addition, the potential for normal tissue toxic...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61K38/19A61K38/21A61K39/395A61N5/10A61P35/00
CPCA61K38/18A61K38/19A61K38/21A61K2039/505A61N2005/1098C07K16/2803A61P35/00A61K39/3955A61K41/0038A61N5/10C07K16/18G01N33/57423G01N33/57484G01N2333/495G01N2333/70503G01N2333/70585G01N2800/52
Inventor R·帕里
Owner VARIAN MEDICAL SYSTEMS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com