A61K2239/26

ANTIGEN-BINDING POLYPEPTIDE TARGETING B7H3 AND APPLICATION THEREOF

The present application relates to an antigen-binding polypeptide that specifically binds to B7H3, comprising at least one complementarity-determining region (CDR) of an antibody heavy chain variable region (VH), wherein the VH comprises an amino acid sequence set forth in SEQ ID NO: 25. The present application further relates to a chimeric antigen receptor comprising the antigen-binding polypeptide and a universal CAR-T cell comprising the chimeric antigen receptor. The CAR-T cell recognizes a surface antigen of a tumor cell and knocks out TCR and HLA-A genes expressed by the cell at the same time, so that the immune rejection caused by an allogeneic CAR-T therapy is reduced, the survival time of the cell is prolonged, and the anti-tumor effect is improved.

INHIBITORY CHIMERIC ANTIGEN RECEPTOR PREVENTS ON-TARGET OFF-TUMOR EFFECTS OF ADOPTIVE CELL THERAPY

Embodiments of the disclosure encompass methods and compositions that enhance adoptive cell therapy by preventing or at least reducing on-target off-tumor effects of adoptive cell therapy. The disclosure concerns an immune effector cells of any type that are engineered to express two separate chimeric molecules: an activating chimeric antigen receptor that activates the immune effector cell through costimulatory domains following binding to a first antigen, and an inhibitory chimeric antigen receptor that inhibits cell-mediated activation upon binding to a second antigen. In specific cases, the inhibitory chimeric antigen receptor prevents fratricide and exhaustion by inhibiting activation of the cell through the activating chimeric antigen receptor when the inhibitory chimeric antigen receptor binds a particular antigen, including one adopted by sibling engineered immune effector cells through trogocytosis.

Natural killer cell lines and methods of use
10138462 · 2018-11-27 · ·

This invention relates to a natural killer cell line termed NK-92 and to NK-92 cell lines that have been modified by transfection with a vector to confer advantageous properties. Additionally, the invention provides an NK-92 cell, an NK-92 cell modified by transfection with a vector conferring advantageous properties, which is unable to proliferate and which preserves the effective cytotoxic activity. The invention provides a modified NK-92 cell line that is transfected with a vector encoding a cytokine that promotes the growth of NK-92 cells. In a significant embodiment, the cytokine is interleukin 2. The invention additionally provides a modified NK-92 cell line that is transfected with a vector that expresses a thymidine kinase gene. The invention further provides a modified NK-92 cell line that is transfected with a vector that expresses a ?.sub.2 microglobulin that has lost the ability to bind to T-cell receptors.

Compositions and methods for treating autoimmune and inflammatory diseases

Compositions and methods are provided for the treatment and/or prevention of an inflammatory and/or autoimmune disease or disorder.

CHIMERIC ANTIGEN RECEPTORS TARGETING HER2
20180326032 · 2018-11-15 ·

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain targeted to HER2, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

PROCESSES FOR PRODUCTION OF TUMOR INFILTRATING LYMPHOCYTES AND USES OF SAME IN IMMUNOTHERAPY
20180325954 · 2018-11-15 ·

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

MATERIALS AND METHODS FOR ENGINEERING CELLS AND USES THEREOF IN IMMUNO-ONCOLOGY

Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

Altering Gene Expression in Modified T Cells and Uses Thereof
20180312848 · 2018-11-01 ·

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

METHODS FOR GENERATING ENGINEERED HUMAN PRIMARY BLOOD DENDRITIC CELL LINES
20180305666 · 2018-10-25 · ·

Provided are engineered primary blood and monocyte-derived dendritic cells, wherein the dendritic cell expresses a functional Tax protein from a T cell leukemia virus, and methods of making and using the same.

TCR AND USES THEREOF

The present invention relates to a TCR or functional variant thereof having antigenic specificity for CD1c molecules associated with a self-lipid, preferably (mLPA) or derivative thereof, to relative polypeptide, protein, nucleic acid, recombinant expression vector, host cell, population of cells, antibody and pharmaceutical composition. The present invention also relates to the uses of said TCR and relative products, in particular for use in the treatment and/or prevention of an hematological disorder.