Yeda Research and Develpment & Co. Ltd

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

The Medical Research, Infrastructure and Health Services Fund of the Tel Aviv Medical Center

Other

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

Biosensor Applications Sweden Ab

The Medical Research Infrastructure and Heal Serviced Fund of the Tel Aviv Medecal Center

Zelig Eshhar

Tova Waks

Gideon Gross

Anat Globerson Levin

Moran Rawet Slobodkin

Daniel Schindler

Steven A Rosenberg

David Wallach

Patrick Hwu

Itamar Willner

Yechiel Shai

Dan S Tawfik

Benjamin Geiger

Eran Elinav

Nir Friedman

Avner Fink

Assaf Marcus

Talia Hahn

Bernard S Green

Naamit Deshet-unger

Shay Yaari

Ben Zion Katz

Ido Laskov

Christopher J Arnush

Dan Grisaru

Shimrit Lieber

Christopher J Arnusch

The present invention provides T-cells modified to express at least two chimeric antigen receptors, wherein one of the CARs binds specifically to an antigen selected from CD138, HER2 and CD24 and another CAR binds specifically a different antigen selected from CD 138, HER2 and CD24. Further, the invention provides pharmaceutical compositions comprising these CAR T-cells and their use in treatment of cancer, in particular, ovarian cancer, DNA constructs encoding said CARs and methods for preparation of T-cells expressing said CARs.

T-cells comprising two different chimeric antigen receptors and uses thereof

The present invention provides T-cells expressing at least two different chimeric antigen receptors, wherein one of the CARs binds specifically to CD138 and another CAR binds specifically to CD38. In particular, the present invention provides T-cells expressing two different CARs, when one CAR comprises anti-CD138 sc Fv and the second CAR anti-CD138 sc Fv. Further, the invention provides a pharmaceutical composition comprising these dual CAR T-cells and their use in treatment of cancer, in particular multiple myeloma, and methods for preparation of these cells.

T-cells comprising anti-CD38 and anti-CD138 chimeric antigen receptors and uses thereof

Methods of culturing T cells are provided. Accordingly there is provided a method of culturing T cells comprising culturing T cells in the presence of a T cell stimulator, an exogenous CCL21 and an exogenous ICAM1, thereby culturing the T cells. Also provided are cell cultures, isolated T cells and uses of same.

Methods of culturing t cells and uses of same

A redirected Treg cell is endowed with specificity toward a selected target antigen or ligand. The cell contains a chimeric receptor polypeptide that is expressed in a single, continuous chain, with an extracellular recognition region displayed on the surface of the cell, a transmembrane region and an intracellular signaling region. The extracellular recognition region is specific for the selected target antigen or ligand. The intracellular signaling region includes a combination of T-cell signaling polypeptide moieties, which combination, upon binding of the extracellular recognition region to the selected target antigen or ligand, triggers activation of the redirected Treg cells to cause suppression of T-cell mediated immunity. Such redirected Treg cells may be used to suppress undesired activity of T effector cells thereby mediating an immune or inflammatory response. They are particularly useful in treating T effector cell-mediated diseases, such as inflammatory bowel disease, transplant rejection and GVH disease.

Redirected, genetically-engineered T regulatory cells and their use in suppression of autoimmune and inflammatory disease

A method of treating a disease, such as cancer, by administering to a subject in need of such treatment an effective amount of allogeneic T cells with a MHC unrestricted chimeric receptor short time after partial lymphodepletion. The method also comprises administering one or more agents that delay egression of the allogeneic T cells from lymph nodes of said subject during adoptive transfer of said allogeneic T cells to the subject by trapping the T cells in the lymph nodes.

Immunotherapy using redirected allogeneic cells

Isolated peptides of 13-30 amino acids comprising 5-9 consecutive repeats of the amino acid pair Alanine-Leucine or Alanine-Valine are provided. The peptides further comprise a stretch of 1-3 Lysine residues present at least at one of the peptide's termini, wherein the only Lysine residue in the isolated peptide is present at the stretch of 1-3 Lysine residues. Pharmaceutical compositions comprising same, methods of treating inflammatory conditions and allergic reactions, as well as methods of neutralizing the activity of lypopolysaccharides are also provided.

Anti-inflammatory peptides and use thereof

Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.

Chimeric receptor genes and cells transformed therewith

A protein comprising an antigen-binding portion formed by two cooperating peptide sequences of FIGS.A andB of the application. The protein may alternatively comprise an altered antigen-binding portion where at least one of the peptide sequences is an altered sequence, an altered sequence being a sequence of FIG.A orB in which one or more of an amino acid residue has been added, deleted or replaced by another amino acid residue. The altered antigen-binding portion retains substantially the same antigen-binding specificity as said antigen-binding portion. Also disclosed are apparatus, systems and methods for detecting small assayed molecules in a sample using the protein.

Detection of small molecules by use of a piezoelectric sensor

A cytotoxic protein expressed by human peripheral blood mononuclear cells is isolated in essentially homogenous form. This protein may be used to elicit production of polyclonal or monoclonal anti-cytotoxin antibodies. Hybridomas secreting anti-cytotoxin antibodies are identified by a solid phase bioassay. The antibodies are useful in the immunopurification of cytotoxins. The purified cytotoxic proteins are useful for the treatment of virus-infected or tumor target cells, either alone or in combination with interferon or a metabolic blocker.

Murine monoclonal antibody binding TNF.alpha.

There are produced recombinant gene pairs which endow mononuclear cells, mainly various lymphocyte type cells, with antibody-type specificity. In specific gene pairs the rearranged gene pairs code for a binding site of an antibody molecule from the same species, of the T-cell receptor gene, or another species. Gene pairs of the invention code, for example, for antibodies specific towards tumor-specific antigens, viral antigens, modified self antigens, bacterial or fungal antigens, autoimmune type disease antigens and the like. The invention further relates to expression vectors for the effective transfection of such cell types comprising such a recombinant gene pair, to methods for producing same and to pharmaceutical compositions comprising as active ingredient an effective quantity of lymphocytes transfected with such gene pairs.

Endowing lymphocytes with antibody specificity

Method for screening catalytic non-enzyme polypeptides and proteins

Growing community of inventors

Rehovot, Israel

Zelig Eshhar