Dana-farber-cancer Institute Inc.

University of Texas System

The University of Tokyo

Coulter Corporation

Toudai Tlo, Ltd.

Y's Ac Co., Ltd.

Chikao Morimoto

Stuart F Schlossman

Kei Ohnuma

Jonathan S Duke-Cohan

Nam Hoang Dang

Christopher E Rudd

Yutaro Kaneko

Taketo Yamada

Norman Letvin

Kohji Yamada

Mutsumi Hayashi

Toshihiro Okamoto

Teruo Inamoto

Mesothelioma growth inhibitory effect of standard cisplatin-pemetrexed concomitant therapy is potentiated by combination with an anti-CD26 antibody. A high therapeutic effect and excellent safety is obtained by the concomitant use of an anti-CD26 antibody and gemcitabine. By conjugating an anti-CD26 antibody (YS110) with triptolide via a divalent cross-linking agent for concomitant therapy using the anti-CD26 antibody, a novel antibody-drug conjugate (Y-TR1) very highly effective for CD26-positive malignant mesothelioma cells has been successfully obtained.

Cancer treatment composition combining anti-CD26 antibody and other anticancer agent

The present invention relates to a therapeutic agent for malignant mesothelioma comprising a substance which inhibits binding of CD26 to extracellular matrix such as an siRNA targeting CD26 cDNA or an anti-CD26 antibody. The present invention also relates to a method of treating malignant mesothelioma, which comprises administering the substance to a patient in need thereof.

Method of treating malignant mesothelioma

The present invention provides methods of identifying a substance that down-regulates or up-regulates an immune response and kits used for the identification methods. A method of this invention comprises detecting a substance that inhibits or enhances the interaction between CD26 and caveolin-1. Another method comprises detecting a substance that inhibits or enhances the interaction between caveolin-1 and Tollip. Still another method comprises detecting a substance that inhibits or enhances the interaction among caveolin-1, Tollip, and IRAK-1. The present invention also relates to immunoregulatory agents comprising a substance that down-regulates an immune response, such as siRNA against caveolin-1 or Tollip. The invention further provides immunoregulatory agents comprising a substance that up-regulates an immune response. These agents are useful for treating inflammatory diseases, autoimmune diseases, or other immune-mediated disorders.

Methods of identifying immunoregulatory agents, immunoregulatory agents, and uses thereof

Therapeutic methods comprising administering anti-CD26 antibodies for the prevention and treatment of cancers and immune diseases associated with expressing CD26 are provided. The invention describes various types of anti-CD26 antibodies and modes of administration.

Anti-CD26 monoclonal antibodies as therapy for diseases associated with cells expressing CD26

Anti-CD26 monoclonal antibodies as therapy for diseases associated with cells expressing CD26.

A soluble form of CD26 isolated from human serum is disclosed. The serum form shares similar enzymatic and antigenic properties with the membrane form. However, in several biochemical aspects there are distinct differences. In particular, the soluble serum form has a molecular weight of 175 kDa (in contrast to the 105 kDa molecular weight of the membrane form), and it does not bind Adenosine Deaminase Type-1. Nevertheless, the soluble form expresses functional dipeptidylpeptidase IV activity and retains the ability to costimulate the T lymphocyte response to recall antigen. Although 105 kDa membrane type CD26 may be found in the serum in small amounts, the majority of serum DPPIV activity is provided by a novel peptidase structurally distinct from membrane C26/DPPIV.

Form of dipeptidylpeptidase IV (CD26) found in human serum

A circulating, soluble form of DPPIV/CD26 isolated from human serum is disclosed. The serum form shares similar enzymatic and antigenic properties with the ubiquitous membrane form. However, in several biochemical aspects there are distinct differences. In particular, the circulating serum form has a molecular weight of 175 kDa (in contrast to the 105 kDa molecular weight of the membrane form), and it does not bind Adenosine Deaminase Type-1. Nevertheless, the circulating form expresses functional dipeptidylpeptidase IV activity and retains the ability to costimulate the T lymphocyte response to recall antigen. Circulating DPPIV has been determined to be the soluble form of a 175 kDa DPPIV CD26-related molecule rapidly expressed on the surface of activated T cells, prior to the expression of 105 kDa CD26. Although 105 kDa membrane type CD26 may be found in the serum in small amounts, the majority of serum DPPIV activity is provided by a novel peptidase structurally distinct from 105 kDa CD26/DPPIV. Polyclonal and monoclonal antibodies capable of distinguishing the 175 kDa form from the 105 kDa form are also disclosed.

Form of dipeptidylpeptidase IV (CD26) found in human serum, antibodies thereto, and uses thereof

A monoclonal antibody which binds preferentially to a subset of the human CD4+ lymphocyte population whereby to positively and precisely distinguish between helper-inducer and suppressor-inducer cells in the CD4+ cell population. The monoclonal antibody recognizes a novel antigen on the CD4+ lymphocytes by means of which it can bind CD4+ cells which express the antigen on the surface of CD4+ cells. The CD4+ subset cell population to which this antibody preferentially binds is the CD4+ helper-inducer population. This selectivity of the monoclonal antibody enables cell sorting, diagnostic and possible therapeutic applications thereof to be realized. The monoclonal antibody also reacts with CD8 cells, B cells and macrophages.

Monoclonal antibody which distinguishes helper inducer and suppressor

A monoclonal antibody which binds preferentially to a subset of the human CD8 lymphocyte population whereby to positively and precisely distinguish between cytotoxic effector and supressor effector cells in the CD8 cell population. The monoclonal antibody recognizes a novel epitope of LFA-1 antigen by means of which it can bind CD8 cells which express the eptope on a surface antigen thereof. The CD8 subset cell population to which this anitbody binds preferentially is the CD8 cytotoxic effector population. This selectivity of the monoclonal antibody enables cell sorting, diagnostic and positive therapeutic applications thereof to be utilized.

Monoclonal antibody specific to a novel epitope of the LFA-1 antigen of

An essentially purified antigen comprising a protein present in the T-cells of Aotus trivirgatus having molecular weights of 140 KD and 105 KD under reducing conditions and 120 KD and 90 KD under non-reducing conditions, antibodies against this antigen, and a method of using these antibodies to activate T-cells. The antibodies are able to induce T-cell activation in synergy with phorbol myristate acetate alone and with antibody against the T 11.sub.3 epitope of T 11 (CD.sub.2) antigen alone.

Activation antigen

A method of distinguishing subsets within a plurality of human cells including producing a monoclonal antibody to a non-human primate cell, contacting the monoclonal antibody with the human cells, and distinguishing the subsets on the basis of different degrees of reactivity with the monoclonal antibody.

Growing community of inventors

Needham, MA, United States of America

Chikao Morimoto