Dana-farber-cancer Institute Inc.

The University of Texas System

University of Michigan

Coulter Corporation

Sidney Farber Cancer Institute, Inc.

Stuart F Schlossman

Chikao Morimoto

Michel Streuli

Paul J Anderson

James Douglas Griffin

Christopher E Rudd

Jonathan S Duke-Cohan

Ellis L Reinherz

Nam Hoang Dang

Thomas F Tedder

Lee M Nadler

Chonghui Zhang

Benedict R Lucchesi

Arnold S Freedman

Haruo Saito

Robert F Todd, Iii

Norman Letvin

Jerome Ritz

Prasad V Kanteti

Paul J Simpson

Mei X Wu

Stefan C Meuer

Thierry Hercend

Zhaohui Ao

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.

The invention features attracting polypeptides and nucleic acids encoding them. The attractin polypeptides are useful for enhancing immune responses.

Regulation of immune responses by attractin

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

The invention provides isolated nucleic acids molecules, designated Siva nucleic acid molecules, which encode proteins involved in immune cell apoptosis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing Siva nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a Siva gene has been introduced or disrupted. The invention still further provides isolated Siva proteins, fusion proteins, antigenic peptides and anti-Siva antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Siva genes, novel genes involved in CD27-mediated apoptosis

A monoclonal antibody which specifically binds to an antigen on the membrane of mitochondria in apoptotic cells. The antigen is a 38 kD protein that is detectable in cells undergoing apoptosis and undetectable in normal cells. This selectivity of the monoclonal antibody provides a method of distinguishing between normal and apoptotic cells in a sample of human hemopoietic cell populations. A method for detecting and measuring cells undergoing apoptosis is also provided.

Monoclonal antibody that detects apoptotic antigen

Methods for interfering with antigen presenting cell-mediated priming of resting peripheral blood T lymphocytes to undergo activation induced cell death ('apoptosis') by inhibiting an interaction between a membrane associated molecule ('an APC apoptotic ligand') present on stimulated antigen presenting cells ('APC') and a counter-receptor that is present on T lymphocytes are disclosed. The antigen presenting cells are preferably from the monocyte/macrophage cell line or are dendritic cells. Also disclosed are methods of screening for inhibitors of APC-mediated priming of T lymphocytes to undergo apoptosis and methods and agents for detecting, identifying and characterizing an APC apoptotic ligand. Inhibitors identified by the screening method of the invention are used to reduce the T lymphocyte depletion associated with HIV infection and thereby mitigate the severe immunodeficiency associated with AIDS by interfering with the association between HIV-infected antigen presenting cells, especially monocytes and macrophages, and T cells.

Inhibition of APC-mediated apoptosis of activated T lymphocytes

A purified preparation of a polypeptide that is immunologically reactive with the monoclonal antibody produced by the hybridoma designated ATCC # HB 10319.

Proteins active in lymphocyte-mediated cytotoxicity

This invention concerns alteration of the interaction of PTKs and T-cell receptors. We have found that PTKs and T-cell receptors are complexed within the T-cell and the formation of this complex dictates the susceptibility of the T-cell to activation and to infection by viruses such as HIV. The nature of the interaction between the kinase and the T-cell receptor in a human is also related to the potential for cancer cell formation in that human, and to susceptibility to an autoimmune disease. Modified p56.sup.lck and transfected mammalian cells expressing the same are disclosed.

Alteration of the interaction of a T-cell receptor with a

An isolated DNA that includes a sequence encoding a polypeptide with which the monoclonal antibody TIA-1 produced by the hybridoma designated ATCC#HB10319 is immunologically reactive; a vector or a cell containing such a DNA; and a method of using such a DNA to identify cytolytic lymphocytes.

DNAS encoding proteins active in lymphocyte-medicated cytotoxicity

DNA encoding a protein active in lymphocyte-mediated cytotoxicity

This invention concerns alteration of the interaction of PTKs and T-cell receptors. We have found that PTKs and T-cell receptors are complexed within the T-cell and the formation of this complex dictates the susceptibility of the T-cell to activation and to infection by viruses such as HIV. The nature of the interaction between the kinase and the T-cell receptor in a human is also related to the potential for cancer cell formation in that human, and to susceptibility to an autoimmune disease. Modified CD4 and CD8 T cell receptors and transfected mammalian cells expressing the same are disclosed.

A hybrid cell line is developed which produces a monoclonal antibody which binds to a unique antigenic site expressed on the surface of phagocytic cells. The monoclonal antibody binds to and activates a specific domain of the CD11b glycoprotein so as to inhibit adhesion dependent functions of the phagocytic cell, but it does not affect other phagocytic functions. This monoclonal antibody can be used as a reactant in an in vitro diagnostic immunoassay for detecting the unique antigenic site on the surface of normal human neutrophils.

Monoclonal antibody which inhibits the adhesion functions of the .beta.

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.

Growing community of inventors

Newton Centre, MA, United States of America

Stuart F Schlossman