Charité – Universitätsmedizin Berlin

Max-delbruck-centrum Fur Molekulare Medizin

Max-delbrück-centrum Für Molekulare Medizin in Der

Helmholtz-gemeinschaft; Charité—universitätsmedizin Berlin

Max-delbruck-centrum Fur Molekulare Medizin in Der Helmholtz-gemeinschaft

Antonio Pezzutto

Thomas Blankenstein

Oliver Schmetzer

Simone Rhein

Özcan Cinar

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer, in particular, of B cell lymphoma or B cell leukemia. The invention provides a nucleic acid encoding TCR alpha or beta chain constructs of TCR constructs capable of specifically binding to a peptide of SEQ ID NO: 1, derived from the lineage specific antigen CD22, in the context of HLA-A2 and to subsequently lyse CD22-positive cells. The invention further provides a corresponding protein and host cell. e.g., a CD8+ T cell, pharmaceutical compositions comprising the same, and therapeutic use for treatment of B cell lymphoma or B cell leukemia, such as diffuse large B-cell lymphoma (DLBCL).

CD22-specific T cell receptors and adoptive T cell therapy for treatment of B cell malignancies

Disclosed herein are adoptive T cell therapies or T cell receptor (TCR) gene therapies from the treatment of cancer. The therapies utilize a nucleic acid encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a MYD88 L265P peptide of SEQ ID NO: 2 in the context of HLA-B*07:02 having a high avidity to said peptide/HLA complex. Proteins corresponding to said TCR constructs and host cells, preferably, CD8+ T cells, comprising the TCR constructs are described, as well as the medical use of such nucleic acids, proteins or host cells, in particular, in the diagnosis, prevention and/or treatment of a MyD88 L265P expressing cancer such as a non-Hodgkin B-cell lymphoma selected from the group comprising diffuse large B-cell lymphoma (DLBCL), e.g., activated B-cell-like DLBCL (ABC-DLBCL) or pCNS DLBCL, cutaneous DLBCL, leg-type DLBCL or testicular DLBCL; lymphoplasmacytic lymphoma (LPL), e.g., Waldenström macroglobulinemia (WM); and IgM monoclonal gammopathy (IgM MGUS).

Specific t cell receptors against epitopes of mutant MYD88L265P protein for adoptive T cell therapy

The present invention is related to a peptide comprising an amino acid sequence according to SEQ. ID. No 1.

Peptides regulating the surface expression of the T cell receptor

Growing community of inventors

Berlin, Germany

Antonio Pezzutto