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Methods of assessing and treating cancer in subjects having dysregulated lymphatic systems

A technology of lymphatic system and subjects, applied in chemical instruments and methods, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve undiscussed problems

Pending Publication Date: 2019-08-30
ENSEMBLE GRP HLDG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these previous studies did not discuss the effect of these antagonists on the progression of established distant metastases after removal of the primary tumor

Method used

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  • Methods of assessing and treating cancer in subjects having dysregulated lymphatic systems
  • Methods of assessing and treating cancer in subjects having dysregulated lymphatic systems
  • Methods of assessing and treating cancer in subjects having dysregulated lymphatic systems

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0211] Example 1 : To evaluate the dysregulated lymphatic system in lung cancer patients treated with PD-1 inhibitor immunotherapy.

[0212] Patients with advanced or metastatic lung cancer are treated with PD-1 inhibitors. Dysfunction of their lymphatic system was evaluated. In one example, VEGF C, VEGF D, or midkine is measured in the patient's serum before or during treatment in the patient for glymphatic system assessment. In other examples, pre-treatment imaging studies and / or similar imaging studies during immunotherapy treatment include computed tomography, MRI, nuclear medicine testing including PET imaging or ventilation perfusion scans.

[0213]In patients with lymphatic system dysregulation ("biomarker positive"), the progression-free survival, overall survival, durable response (durable response), and response evaluation criteria in solid tumors (RECIST 1.1) and immune-related response criteria (irRC) objective Response measures, both showed significant deterio...

Embodiment 2

[0237] Example 2 - Treatment of advanced and metastatic lung and breast cancer with modulators of lymphobiology plus immunotherapy resulted in improved outcomes.

[0238] Syngeneic mice (C57Black 6 and BALB / c) were implanted subcutaneously with 1 to 2 million LLC lung cancer cells or 4T1 breast cancer cells. Animals were treated with either chemotherapy (cisplatin) or immunotherapy (anti-PD-1 mAb) alone, with vehicle alone as a control group. Imaging animals with intravascular ultrasound (IVUS), CT / PET or MRI to detect primary tumor growth and metastatic spread of tumors. Blood samples were taken for multiplex measurement of serum biomarkers of lymphoid biological function (Millipore mouse 24plex; MAGPMAG-24K). On study day 10, animals were injected with 1-1.5 million tumor cells in the tail vein. Between study days 13 and 16, primary tumors were surgically excised and animals resumed treatment.

[0239] Treatment arms included (1) anti-PD-1 mAb alone; (2) anti-PD-1-mAb p...

Embodiment 3

[0247] Treatment with lymphatic system modulators and immunomodulators or chemotherapy significantly improved objective outcomes in mice with dysregulated lymphatic system advanced or metastatic cancer in animal experiments and prevented progression to cancerous lymphadenitis, This is a form of severe lymphatic dysregulation in cancer patients.

[0248] The experiments of Example 2 were performed in syngeneic mice using the same animal models (4T1 and LLC). Another group of tumor cells was transfected to overexpress VEGF-C to stimulate severe lymphoid dysregulation. Overexpression of VEGF C by tumor cells can lead to severe lymphatic vessel dysregulation and extremely aggressive cancerous lymphangitis, a subset of the group of dysregulated lymphoid lesions that are resistant to immunotherapy (Example 1). Both objective and immune / functional outcomes were significantly improved when treated with lymphatic system modulators (Example 2). In this experiment, it was assessed whet...

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PUM

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Abstract

Provided herein is a method for determining cancer treatment using an immune modulating therapy in a subject in need thereof. The method comprises assessing whether a lymphatic system in a subject isdysregulated. When the lymphatic system is dysregulated, a treatment for the lymphatic system is determined before a therapeutic amount of an immune modulating therapy is administered to treat cancerin the subject. Alternatively, when the lymphatic system is dysregulated, an immune modulating therapy is selected to treat cancer in the subject, which immune modulating therapy is independent of immune-cell priming, antigen trafficking, antigen presentation, and any combination thereof. The subject may also be treated for cancer accordingly.

Description

[0001] cross reference [0002] The statement of this application requires the U.S. Provisional Application No. 62 with the title of "Methods of Determining treatment with Immune Modulating Therapies in Cancer Subjects" submitted on September 26, 2017 / 399,766; and the invention titled "Methods of Treating Cancer Subjects with Immune Modulating Therapies and Regulators of Lymphatic Biology" submitted on October 25, 2017 U.S. Provisional Application No. 62 / 124,488," both of which are hereby incorporated by cross-reference in their entirety and in their entirety for the benefit of their filing dates. technical field [0003] This disclosure relates to the field of cancer diagnosis and treatment, in particular the administration of immunomodulatory therapy for cancer in subjects with disorders of the lymphatic system. Background technique [0004] Patients with disorders of the lymphatic system are unresponsive to immunomodulatory therapies, which must rely on immune cell prim...

Claims

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Application Information

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IPC IPC(8): A61K39/395
CPCC07K16/22A61K2039/505A61K2039/507A61K2039/545C07K2317/76A61P35/00C07K16/2818A61K31/4375A61B5/055A61B5/418A61B6/032A61B6/037
Inventor M·D·库奥C-Y·黄
Owner ENSEMBLE GRP HLDG
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