Anti-TMEM-180 antibody, anticancer drug and cancer testing method
Inventors
Matsumura, Yasuhiro • Yasunaga, Masahiro • Saijou, Shinji • Hanaoka, Shingo • Anzai, Takahiro • Manabe, Shino
Assignees
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Publication Number
US-11633499-B2
Publication Date
2023-04-25
Expiration Date
Abstract
An object of the present invention is to provide an anticancer drug capable of treating cancer by finding a target molecule specifically expressed in cancer cells and by specifically acting on the target molecule, and to provide a cancer testing method including a step of measuring the target molecule in a sample. The present invention provides an anticancer drug containing, as an active ingredient thereof, an anti-transmembrane protein 180 (TMEM-180) antibody or an antigen-binding fragment thereof. In addition, the present invention provides a cancer testing method including a step of measuring the amount of TMEM-180 in a sample collected from a subject.
Core Innovation
The invention relates to diagnosing colon cancer in a human subject by detecting the existence or amount of exosomes having TMEM-180, or by detecting the existence or amount of TMEM-180 expression on exosomes, in a body fluid sample obtained from the subject. The body fluid is a blood sample, and the detection is performed with an antibody binding to transmembrane protein 180 (TMEM-180) or an antigen-binding fragment thereof.
The presence of exosomes having TMEM-180 and/or TMEM-180 expression on exosomes indicates that the human subject has a colon cancer secreting exosomes presenting TMEM-180 to the body fluid. The approach uses antibody binding to TMEM-180 to detect TMEM-180 on exosomes rather than relying on TMEM-180 in isolation.
The antibody is defined by specific heavy chain CDR1, CDR2, and CDR3 sequences and specific light chain CDR1, CDR2, and CDR3 sequences, and the antigen-binding fragment includes corresponding heavy and light chain variable region features. The disclosure further references antibody clone embodiments for anti-TMEM-180 antibodies, including Clone 129, Clone 382, Clone 1361, Clone 98, Clone 101, Clone 212, clone 669, clone 1052, and clone 1105, with described CDR regions and SEQ ID numbers.
Claims Coverage
The independent claim coverage centers on diagnosing colon cancer by detecting TMEM-180-positive exosomes or TMEM-180 expression on exosomes in a blood sample using a TMEM-180-binding antibody or antigen-binding fragment. The inventive features are the exosome/TMEM-180 detection as the diagnostic indicator and the specific antibody structure defined by heavy- and light-chain CDR sequences, with further refinement by heavy- and light-chain variable region sequences.
Diagnosing colon cancer by detecting TMEM-180 on exosomes
A method of diagnosing colon cancer in a human subject comprising detecting the existence or amount of exosomes having TMEM-180, or detecting the existence or amount of TMEM-180 expression on exosomes, in a body fluid sample obtained from the human subject using an antibody binding to transmembrane protein 180 (TMEM-180) or an antigen-binding fragment thereof, wherein the body fluid is a blood sample and exosomes having TMEM-180 and TMEM-180 expression on exosomes indicate colon cancer secreting exosomes presenting TMEM-180.
Antibody defined by specified heavy- and light-chain CDR sequences
The antibody and the antigen-binding fragment each comprise a heavy chain variable region having a heavy chain CDR1 having DYWVS (SEQ ID NO: 72), a heavy chain CDR2 having EIYPNSGATNFNENFK (SEQ ID NO: 73), and a heavy chain CDR3 having DGTMGIAYYFDY (SEQ ID NO: 74), and a light chain variable region having a light chain CDR1 having KASQNINRYLN (SEQ ID NO: 75), a light chain CDR2 having NANSLQT (SEQ ID NO: 76), and a light chain CDR3 having LQHNSWPYT (SEQ ID NO: 77).
Antibody refinement by specified heavy- and light-chain variable region sequences
The method wherein the antibody and the antigen-binding fragment each comprise a heavy chain variable region having SEQ ID NO: 78 and a light chain variable region having SEQ ID NO: 79.
Coverage is centered on diagnosing colon cancer by detecting TMEM-180-presenting exosomes, or TMEM-180 expression on exosomes, in a blood sample using a TMEM-180-binding antibody or fragment defined by specified heavy- and light-chain CDR sequences and further refined by particular heavy- and light-chain variable region sequences.
Stated Advantages
TMEM-180 detection is described as having specificity versus conventional markers such as CEA.
TMEM-180 detection is described as providing improved sensitivity for detecting recurrence.
TMEM-180 targeting is described as enabling targeted delivery to TMEM-180-expressing cancer cells, including use in antibody-drug conjugates (ADCs).
Documented Applications
Diagnosing colon cancer in a human subject by detecting the existence or amount of exosomes having TMEM-180, or TMEM-180 expression on exosomes, in a blood sample.
Monitoring colon cancer recurrence/metastasis by using TMEM-180-positive exosomes for improved sensitivity detection.
Using anti-TMEM-180 antibodies and antigen-binding fragments as anticancer drug components, including targeted delivery such as antibody-drug conjugates (ADCs).
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