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Markers selectively deregulated in tumor-infiltrating regulatory t cells

a tumor-infiltrating regulatory and t cell technology, applied in the direction of immunodeficiency, drug composition, peptides, etc., can solve the problems of poor prognosis, and achieve the effect of confirming the relevance of these signatures, specific and safer modulation of treg cells, and better understanding of treg functional roles

Inactive Publication Date: 2019-12-26
CHECKMAB SRL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

The patent text describes the invention of a method for identifying and manipulating tumor-infiltrating Treg cells in cancer patients. This can help to improve immunotherapy and identify new targets for cancer treatment. The invention also describes the use of antibodies to enhance the immunotherapy of cancer by targeting Treg cells. The patent also describes a method for screening for marker activity modulators, which can identify agents that directly or indirectly modulate marker activity. The patent also describes the use of marker inhibitors to increase the number of T-cells in an organism and decrease the number of T-cells in tumors. The methods of the invention can be applied to any organism that contains T-cells that express the marker.

Problems solved by technology

Remarkably, high expression in whole tumor samples of Treg signature genes, such as LAYN, MAGEH1 or CCR8, correlated with poor prognosis.

Method used

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  • Markers selectively deregulated in tumor-infiltrating regulatory t cells
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  • Markers selectively deregulated in tumor-infiltrating regulatory t cells

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Embodiment Construction

[0185]Experimental Procedures

[0186]Human Primary Tissues

[0187]Primary human lung or colorectal tumors and non-neoplastic counterparts were obtained respectively from fifteen and fourteen patients who underwent surgery for therapeutic purposes at Fondazione IRCCS Ca' Granda, Policlinico or San Gerardo Hospitals (Italy). Records were available for all cases and included patients' age at diagnosis, gender, smoking habit (for lung cancer patients), clinicopathological staging (Sobin et al., 2009), tumor histotype and grade (Table II). No patient received palliative surgery or neoadjuvant chemo- and / or radiotherapy. Informed consent was obtained from all patients, and the study was approved by the Institutional Review Board of the Fondazione IRCCS Ca' Granda (approval n. 30 / 2014).

[0188]Non-small-cell lung cancer (NSCLC) were cut into pieces and single-cell suspensions were prepared by using the Tumor Dissociation Kit, human and the gentleMACS™ Dissociator (Miltenyi Biotech cat. 130-095-9...

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Abstract

The present invention discloses a number of markers selectively deregulated in tumor-infiltrating regulatory T cells. The invention relates to molecules able to modulate the expression and / or function of at least one such marker for use in the prevention and / or treatment of the tumor. Preferably the molecule specifically binds to the marker and induces antibody-dependent cell-mediated cytotoxicity (ADCC). The invention further relates to a molecule able to modulate the expression and / or function of at least one such marker for use in a method for in vivo depleting tumor-infiltrating regulatory T cell in a subject, or for use in a method to enhance tumor immunity in a subject. Corresponding pharmaceutical compositions are also contemplated.

Description

RELATED APPLICATION[0001]This application is a national stage filing under 35 U.S.C. § 371 of International Application Serial No. PCT / EP2017 / 061642, filed May 15, 2017, the contents of which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to a molecule able to modulate the expression and / or function of at least one marker that is selectively deregulated in tumor-infiltrating regulatory T cell or to a molecule capable of specifically binding to at least one marker that is selectively deregulated in tumor-infiltrating regulatory T cell and inducing antibody-dependent cell-mediated cytotoxicity (ADCC) for use in the prevention and / or treatment of cancer or for use in a method for in vivo depleting tumor-infiltrating regulatory T cell in a subject or for use in a method to enhance tumor immunity in a subject and relative pharmaceutical composition.BACKGROUND OF THE INVENTION[0003]The combination of genetic mutations and epig...

Claims

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Application Information

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IPC IPC(8): G01N33/574A61K45/06C07K16/28C07K16/30C07K14/47C12N15/113
CPCC07K16/30C07K14/4748C07K16/2866C12N2310/14G01N33/57492C12N15/1138C07K2317/732C12N2310/11C12N15/1135C07K2317/76A61K45/06C12N5/0637A61P35/00A61P35/04A61P37/04A61P43/00A61K35/17A61K31/7088C12N15/113A61K38/00
Inventor ABRIGNANI, SERGIOPAGANI, MASSIMILIANO
Owner CHECKMAB SRL
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