The technology relates in part to methods for controlling the activity or elimination of therapeutic cells using multimerization of proteins to manipulate individual protein-protein interactions in therapeutic cells, for example, by activating or eliminating cells used to promote engraftment, to treat diseases or condition, or to control or modulate the activity of therapeutic cells that express chimeric antigen receptors or recombinant T cell receptors.

The present invention relates, in part, to chimeric protein complexes including an anti-Clec9A targeting moiety, a modified Fc domain, and a modified human IFNα and their use as therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the chimeric protein complexes and their use in the treatment of various diseases.

The present invention relates to compositions and methods for treating cancer, particularly to agents that inhibit the expression and/or activity of the protein second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (SMAC/Diablo). The inhibiting agents include RNA interference molecules silencing the expression of SMAC/Diablo and peptides modulating its interactions within the cell nucleus and mitochondria. The methods and agents of the present invention are useful in treating cancers associated with overexpression of SMAC/Diablo.

Provided are a PD-1 CAR NK-92 cell and a preparation method and use thereof. The PD-1 CAR NK-92 cell expresses PD-1-CD8™-4-1BB-CD3ζ fusion protein in NK-92 cells. The PD-1 CAR NK-92 is obtained by infecting an NK92 cell line with a PD-1 CAR molecule and obtaining monoclonal cells by means of flow screening, and culturing and expanding CAR NK92 monoclonal cell strains with stable traits and a high killing activity. The cells can be produced on a large scale, can be used in different patients without GVHR rejection, and have a specific killing activity and significant therapeutic effect on tumors.

Disclosed are methods for conditionally immortalizing stem cells, including adult and embryonic stem cells, the cells produced by such methods, therapeutic and laboratory or research methods of using such cells, and methods to identify compounds related to cell differentiation and development or to treat diseases, using such cells. A mouse model of acute myeloid leukemia (AML) and cells and methods related to such mouse model are also described.

The invention relates to a peptide comprising the amino acid sequence LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRP, wherein the amino acids in said amino acid sequence are D-amino acid residues, and to methods for the use of this peptide in the treatment of age-related disorders.

An object of the present invention is to provide a novel cyclic peptide compound excellent in cell membrane permeability, a method for producing the same, a composition for screening use, and a method for selecting a cyclic peptide compound that binds to a target substance. According to the present invention, a peptide compound represented by Formula (1) or a salt thereof is provided. In the formula, the symbols have the meanings as defined in the specification of the present application. ##STR00001##

The present disclosure provides novel cell permeant polypeptides and pharmaceutical compositions thereof, and methods for using such polypeptides and pharmaceutical compositions for various therapeutic uses. The present disclosure more specifically provides polypeptides for restoring endothelial function.

A protein-based peptide drug carrier derived from the tetramerization domain of the chimeric oncogenic protein Bcr/Abl of chronic myeloid leukemia. Peptides to be delivered are grafted to the N-terminal helical region of Bcr/Abl tetramer. To facilitate cellular uptake, an Arg-repeating hexapeptide is added to the C-terminal end of the Bcr/Abl protein. The protein-based delivery strategy provides a clinically viable solution to p53-inspired anticancer therapy and is applicable to the development of many other peptide therapeutics to target other intracellular protein-protein interactions responsible for disease initiation and progression.

The presently disclosed subject matter provides polypeptide compositions comprising a chimeric antigen receptor (CAR) that targets mesothelin; and a dominant negative form of programmed death 1 (PD-1 DN). Also provided are immunoresponsive cells comprising such polypeptide compositions and uses of the polypeptide compositions and immunoresponsive cells for treatment, e.g., for treating solid tumors.