Chemotherapeutisches Forschungsinstitut Georg-speyer-haus

Drk Blutspendedienst Baden-wurttemberg-hessen Ggmbh

Chemotherapeutisches Forschunginstitut Georg-speyer-haus

Chemotherapeticshes Forshungsinstitut Georg-speyer-haus

Winfried Wels

Kurt Schönfeld

Congcong Zhang

Christiane Knopp

Christiane Schönfeld

Torsten Tonn

Manuel Grez

Benjamin Daelken

Manuel Kaulich

Sylvia E Schwarz

Anja Waldmann

The present invention pertains to methods and compounds useful in a therapy involving the administration of immune cells to a patient. The method of the invention involves the modification of cells of the immune system with agonists or antagonists of immune regulators such as Interleukin-10 (IL-10) or IL-6, in order to enhance and improve the immunological potential of the immune cells for therapy. Cells modified according to the method of the invention can be administered to a patient to support a treatment of proliferative diseases such as cancer or autoimmune disorders.

Methods and compounds for improved immune cell therapy

The present invention relates to multi-functional proteins which comprise (i) a signal peptide, (ii) a target specific recognition domain, (iii) a linker region, connecting domain (ii) and domain (iv) which comprises a specific modified hinge region of the human CD8 alpha-chain, and (iv) an effector domain. The present invention furthermore relates to nucleic acids encoding the proteins, expression constructs for expressing the protein in a host cell and host cells. The proteins of the invention are chimeric antigen receptors with an optimized linker or hinge region that are suitable for generating target-specific effector cells, for use as a medicament, in particular in the treatment of cancer and in adoptive, target-cell specific immunotherapy.

Chimeric antigen receptors with an optimized hinge region

The present invention relates to an ErbB2-specific NK-92 cell or cell line containing a lentiviral vector encoding a chimeric antigen receptor and preferably two vector integration loci in its cellular genome. The present invention further relates to the use of the ErbB2-specific NK-92 cell or cell line in the prevention and/or treatment of cancer, preferably ErbB2-expressing cancers. The present invention further relates to the use of the ErbB2-specific NK-92 cell or cell line as targeted cell therapeutic agent and/or for adoptive cancer immunotherapy. The present invention further relates to a method for generating an ErbB2-specific NK-92 cell or cell line as well as to a method for identifying an ErbB2-specific NK-92 cell or cell line and to the ErbB2-specific NK-92 cell or cell line obtained or identified by the methods as well as their uses.

CAR-expressing NK-92 cells as cell therapeutic agents

The present invention relates to the use of interleukin-15 (IL-15) as selectable marker for gene transfer, preferably of at least one gene of therapeutic interest, into a mammalian cell or cell line, in particular a human cell or cell line. The present invention furthermore relates to transgenic mammalian cells or cell lines expressing IL-15 as selectable marker and co-expressing at least one protein of interest encoded by at least one gene of interest, which is preferably a protein of therapeutic interest. The present invention is in particular suitable for chimeric antigen receptors (CARs) as the gene or protein of interest and their expression in lymphocytes. The transgenic mammalian cells and cell lines are furthermore suitable for use as a medicament, in particular in the treatment of cancer and in immunotherapy, such as adoptive, target-cell specific immunotherapy.

Interleukin 15 as selectable marker for gene transfer in lymphocytes

Car-expressing NK-92 cells as cell therapeutic agents

Object matter of the invention is an optimized DNA sequence encoding the scFv(FRP5) antibody fragment. This novel sequence prevents the generation of the undesired by-product in the context of an scFv(FRP5)-ETA fusion protein, and possibly also other bacterially expressed scFv(FRP5)-containing fusion proteins. The DNA sequence of the scFv(FRP5) domain of scFv(FRP5)-ETA was modified by exchanging a distinct codon, thereby preventing an otherwise possible internal start of protein translation.

Optimized DNA sequence of an antibody to improve quality and yield of bacterially expressed antibody fusion proteins

Growing community of inventors

Frankfurt am Main, Germany

Winfried Wels