The University of Tokyo

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Chugai Seiyaku Kabushiki Kaisha

Tokyo University of Science Foundation

Telik, Inc.

Chugai Pharmaceutical Co.

Other

The United States of America as Represented by the Department of Health

Sanwa Kagaku Kenkyusho Co., Ltd.

Ono Pharmaceutical Co., Ltd.

Toray Industries, Inc.

The United States of America as Represented by the Secretary of

Dainippon Pharmaceutical Company, Limited

Kureha Chemical Industry Company, Limited

Sbi Pharmaceuticals Co., Ltd.

Kouji Matsushima

Yoshiro Ishiwata

Shoji Yokochi

Hugo O Villar

Edgardo Laborde

Yukiharu Matsumoto

Louise Robinson

Fanying Meng

Brian T Peterson

Steven E Anuskiewicz

Hideaki Inagaki

Masayuki Tsuchiya

Takahito Jomori

Takuji Kakigami

Teizo Yoshimura

Satoshi Ueha

Koh Sato

Ettore Appella

Yoshiki Yamada

Edward J Leonard

Stephen D Showalter

Tatsumi Yamazaki

Yoshihiro Matsumoto

Arya Biragyn

Shiro Shibayama

Satoru Ito

Joost J Oppenheim

Junichi Yamagishi

Masaaki Yamada

Ryuji Furuta

Wenli Ma

Akiyoshi Saitoh

Joost Oppenheim

Yuya Terashima

Etsuko Toda

Dolgor Baatar

Shungo Deshimaru

Chang-Yu Chen

Kouji Kuno

Shinichi Hashimoto

Tohru Tanaka

Jun Abe

Shuichi Kaneko

Kiwamu Takahashi

Motowo Nakajima

Yuichi Hirata

Hidenori Ito

Fuminori Abe

Kenji Yoshida

Masanobu Naruto

Kunitaka Hirose

Mitsuaki Takeuchi

Shin-ichi Hashimoto

Junkoh Yamashita

Tetsuya Matsumoto

Sosuke Yoshinaga

Yuji Ishikawa

Yoshitake Sano

Kunihisa Baba

Hiroaki Terasawa

Katsumasa Tanaka

Masayuki Okamoto

Mikiya Otsuji

Takashi Nakamura

Yusuke Shono

Atsushi Miyachi

Kazuyuki Ojima

Michinori Hakozaki

Dolgor Bataar

Eiji Inoguchi

Meiji Itakura

Keiko Ishioka

Yukako Ishida

Kiyonobu Ikeda

Shigeyuki Shichino

Hiroyasu Aoki

Disclosed are a novel therapeutic means effective and practical against cancer, and a novel substance useful as such a therapeutic means. Provided are novel peptides derived from a partial region of HMGN1, HMGN2, HMGN4 or HMGN5, and anti-cancer agents and anti-cancer effect enhancers containing the peptide as an active ingredient. The peptide of the present invention has an anti-tumor effect even independently, and exerts a remarkably excellent anti-tumor effect particularly when used in combination with an immune checkpoint regulator, or an anti-CD4 antibody or antigen-binding fragment thereof.

HMGN partial peptide and cancer therapy using the same

Novel means that enables prediction of prognosis of a patient with cancer or inflammatory disease is disclosed. In the method for prediction of prognosis of a patient with cancer or inflammatory disease according to the present invention, the expression level of the FROUNT gene in a sample collected from the patient is measured. Since FROUNT is a poor prognostic factor, the lower the expression level of the FROUNT gene is, the better the prognosis in the patient is predicted to be. Or, the expression level of the CC chemokine receptor/ligand gene in a sample collected from the patient is measured. Since the CC chemokine receptor/ligand gene such as CCR2 or CCR5 is a good prognostic factor, the higher the expression level of the CC chemokine receptor/ligand gene is, the better the prognosis in the patient is predicted to be.

Method for predicting prognosis of patient with cancer or inflammatory disease

Disclosed is a means for reducing side effects of an immune checkpoint regulator that is used as an anticancer drug or the like. A side-effect reducing agent according to the present invention comprises as an effective ingredient an anti-CD4 antibody having a high cytotoxic activity, or an anti-CD4 antibody or antigen-binding fragment thereof which antibody or fragment comprises a cytotoxic component bound thereto. The anti-CD4 antibody is a human-type chimeric antibody, humanized antibody or human antibody against human CD4. The immune checkpoint regulator may be, for example, an anti-PD-L1 antibody, an antagonistic anti-CTLA-4 antibody, or an agonistic anti-OX40 antibody.

Method for reducing side effects of immune checkpoint control agent

Means that enables monitoring of an anticancer effect of an anti-CD4 antibody or an anticancer drug targeting an immune checkpoint is disclosed. The method for testing a therapeutic effect of a cancer therapy of the present invention is a method for testing a therapeutic effect of an anticancer drug comprising as an effective ingredient an anti-CD4 antibody or an anticancer drug targeting an immune checkpoint, which method comprises investigation of expression of (1) at least one immune checkpoint receptor, (2) CD8, and (3) at least one cell surface molecule selected from the group consisting of CD44 and CD45RO, on T cells using a sample derived from a patient who received the anticancer drug. Induction of a T cell population which is positive for the immune checkpoint molecule (1) and positive for CD8, and which shows high expression of CD44 and/or high expression of CD45RO, indicates that said anticancer drug is producing a therapeutic effect in said patient.

Method for assessing therapeutic effect of anti-cancer agent having anti-CD4 antibody as active ingredient

The present invention relates to a method of analyzing a composition of nucleic acids derived from a single cell using a microplate including a plurality of reaction wells, the microplate having one bead arranged in one reaction well, the one bead having bound thereto a plurality of molecules of single-stranded oligonucleotides, the single-stranded oligonucleotides each having a nucleic acid capture sequence exposed at the 3' end and a barcode sequence on the 5&#x2032; side of the nucleic acid capture sequence, the barcode sequence including a base sequence that differs from bead to bead.

Method for analyzing nucleic acid derived from single cell

An agent according to the present invention comprises as an effective component any of (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate; (2) a pharmaceutically acceptable salt of (1); or (3) a solvate of (1) or (2), and is used for inhibition of interaction between CR2B or CCR5 and FROUNT protein, inhibition of macrophages, control of cells constituting a cancer microenvironment or inflammatory microenvironment, or enhancement of anticancer activity of an anticancer drug. It is also possible to provide a compound with a reduced side effect and an increased pharmacological effect by identifying a disulfiram derivative having a lower aldehyde dehydrogenase-inhibiting activity and a higher FROUNT-inhibiting activity among derivatives prepared by structural modification of disulfiram.

Agent for controlling cells constituting cancer microenvironment or inflammatory microenvironment

The instant invention provides methods and compositions for modulation of the immune system. Specifically, the present disclosure provides methods and compositions for increasing T cell mediated immune response useful in the treatment of cancer and chronic infection.

Methods and compositions for modulating immune tolerance

An object of the present invention is to provide a preventive and/or therapeutic agent for radiation damage that has a novel mechanism of action and can prevent and alleviate a wide range of symptoms of radiation damage for which no therapeutic measures have been available so far, and moreover, is highly safe to humans. A preventive and/or therapeutic agent for radiation damage comprising a compound represented by the following formula (I) such as 5-aminolevulinic acid (5-ALA) or a salt thereof as an active ingredient can be used to improve the survival rate, improve body weight reduction, and alleviate hematopoietic disorder: (wherein Rrepresents a hydrogen atom or an acyl group; and Rrepresents a hydrogen atom, a linear or branched alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group).

Prophylactic and/or therapeutic agent for radiation damage

The instant invention provides methods and compositions for modulation of the immune system. Specifically, the invention provides methods and compositions for increasing T cell mediated immune response useful in the treatment of cancer and chronic infection.

The object of the invention is to provide an immunological reconstitution promoter or a prophylactic agent for infections for use in allogeneic hematopoietic stem cell transplantation therapy for tumors. The promoter or prophylactic agent enables the amelioration of delayed immune reconstitution or the prevention of infection following transplantation, while maintaining the GVT effect of allogeneic hematopoietic stem cell transplantation. Specifically, in a transplant patient in whom immune reconstitution is delayed, such reconstitution can be promoted by administering, at an early stage following transplantation, a substance capable of depleting CD4cells. Early completion of infection management in the patient and improvement in the survival rate are anticipated as a result. In addition, the risk of complications associated with allogeneic hematopoietic stem cell transplantation is reduced, enabling more widespread use of this therapy.

Immunological reconstitution promoter or prophylactic agent for infections each of which maintains graft-versus-tumor effect

Purified immunocytes were analyzed for expression frequencies, and the NKIR gene expressed specifically in natural killer (NK) cells was successfully identified. The NKIR gene encodes a receptor. Agonists and antagonists for the receptor can be identified by using the receptor.

Proteins expressed in NK cells

Concerning intracellular signal transduction mechanism, there has been drawn a novel hypothesis that, even in the case where phosphorylation does not occur in the intracellular C-terminal domain of a receptor, an unknown molecule associates with the Pro-C terminal domain of a G protein-coupled receptor for each chemokine and thus leukocyte chemotaxis depending on the receptor is controlled. To examine this hypothesis and clarify therapeutic targets in inflammatory diseases as well as other various diseases, attempts are made to search for a CCR2-binding protein. As a result, a novel cytoplasmic protein associating directly and specifically with the Pro-12-C-terminal domain of CCR2 is found out and it is clarified that this protein forms clusters with CCR2 after stimulation with CCL2. Thus, it is confirmed that there is a novel signal transduction system in the G protein relating signal transduction in the CCL2-CCR2 pathway. It is also found out that this novel protein associates with the intracellular C-terminal domain of a receptor CCR5 too.

Molecule associating with intracellular C-terminal domain of receptor

Compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephrtitis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection; pharmaceutical compositions comprising these compounds; and the use of these compounds and compositions in the prevention or treatment of such diseases.

Antagonists of MCP-1 function and methods of use thereof

Growing community of inventors

Tokyo, Japan

Kouji Matsushima