Compositions and methods for reducing MHC class II protein expression in a cell comprising genetically modifying CIITA for use e.g., in adoptive cell transfer therapies.

The invention relates to a T cell receptor (TCR) which is HIV-1 specific and HLA-E restricted. Particularly, the TCR is capable of binding to a peptide of RMYSPTSIL or a peptide of RMYSPTSIL in complex with HLA-E, or a peptide of ILVESPAVL or a peptide of ILVESPAVL in complex with HLA-E. The invention also relates to a nucleic acids and vector encoding the TCR.

The current disclosure fulfills a need in the art by providing methods and compositions for treating and vaccinating individuals against cancer. Accordingly, aspects of the disclosure relate to an isolated peptide comprising at least 70% sequence identity to a peptide of Table 1. In some embodiments, the peptide comprises at least 6 contiguous amino acids of a peptide of Table 1. Further aspects relate to pharmaceutical compositions comprising the isolated peptide, nucleic acids encoding the peptide, and expression vectors and host cells comprising the nucleic acids of the disclosure. Also provided is an in vitro isolated dendritic cell comprising a peptide, nucleic acid, or expression vector of the disclosure.

An object is to provide a PRAM-binding molecule. This object is achieved by a PRAM-binding molecule comprising a heavy-chain variable region containing a heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 1, a heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 2, and a heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 3, and/or a light-chain variable region containing a light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 9, a light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 10, and a light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 11.

Compositions and methods for reducing HLA-A protein expression in a cell comprising genetically modifying HLA-A for use e.g., in adoptive cell transfer therapies.

The present invention relates to tumor antigens encoded in a 5-upstream open reading frame (uORF) within the 5 UTR of different mRNAs. Compositions and peptides comprising such tumor antigens and a virus encoding such tumor antigens are provided. The present invention also relates to the use of such compositions, peptides and viruses in the treatment of cancer.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Provided are TCRs (e.g., TCRs that bind to NY-ESO-1), cells and pharmaceutical compositions comprising these TCRs, nucleic acids encoding these TCRs, expression vectors and host cells for making these TCRs, and methods of treating a subject using these TCRs.

Provided herein are T-cell receptors (TCRs) that when expressed recombinantly on the surface of a T cell are able to recognize the MAGE-B2-derived peptide GVYDGEEHSV (SEQ ID NO: 1) when presented by HLA-A*02:01 sufficiently to activate the recombinant T cell. Certain TCRs provided herein also are able to recognize the MAGE-A4-derived peptide GVYDGREHTV (SEQ ID NO:2) sufficiently to activate the recombinant T cell. Importantly, exemplary TCRs provided herein were thoroughly screened for lack of cross-reactivity with similar peptides that may be presented by normal cells or tissue and for alloreactivity.

The present disclosure provides novel artificial antigen presenting cells (aAPCs). The aAPCs disclosed herein comprise a liposome comprising a phospholipid and a stimulatory ligand displayed on the outer surface of the liposome. The aAPCs of the present disclosure can be used as an off the shelf tool to activate and expand a T cell of interest. Also, the present disclosure provides methods of activating a T cell and manufacturing a T cell therapy product using the aAPCs disclosed herein.