The present invention is in the field of immunology and provides a cell line for the discovery and engineering of T cell receptors. The invention further provides methods for the discovery of antigen-specific T cell receptors and for the engineering of T cell receptors with optimized antigen-binding and antigen-induced signaling properties.

Engineered T cell receptor (TCR) sequences, cells expressing such sequences and methods of use thereof are provided. The engineered receptors are mutagenized in vitro, and selected for target activation potency in combination with selection for a pMHC affinity that is sufficiently low to reduce off-target cross-reactivity. In some embodiments the engineered TCR recognizes the tumor associated antigen (TAA), human MAGE-A3

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

The technology relates in part to methods for inducing partial apoptosis of cells that express an inducible caspase polypeptide. The technology further relates in part to methods for inducing partial apoptosis of cells that express an inducible modified caspase polypeptide, having a modified dose response curve to the multimeric ligand inducer. The technology also relates in part to methods for cell therapy using cells that express the inducible caspase polypeptide or the inducible modified caspase polypeptide, where the proportion of caspase polypeptide-expressing cells eliminated by apoptosis is related to the administered amount of the multimeric ligand inducer.

Provided is a method for isolating and proliferating autologous cancer antigen-specific CD8.sup.+ T cells, and more particularly, a method for selecting an epitope recognized by CD8.sup.+ T cells from autologous cancer antigens present in blood of individual cancer patients; and isolating autologous cancer antigen-specific CD8.sup.+ T cells by using a peptide of the selected epitope, and a method of massively proliferating CD8.sup.+ T cells by using the method. According to the present invention, it is possible to isolate autologous cancer antigen-specific CD8.sup.+ T cells by using the peptide of the CD8 T cell epitope of the autologous cancer antigen present in blood of individual cancer patients instead of a heterologous antigen. Therefore, by using T cells recognizing the autologous cancer antigen, it is possible to effectively select and eliminate cancer cells derived from the cancer patient's own cells. Thus, T cells can be applied to treatment and alleviation of cancer diseases without side effects.

The present invention relates to T cell receptors (TCRs) which bind the HLA-A*02 restricted peptide GLYDGMEHL (SEQ ID NO: 1) derived from the MAGE-A10 protein. The TCRs of the invention demonstrate excellent specificity profiles for this MAGE epitope. Also provided are nucleic acids encoding the TCRs, cells engineered to present the TCRs, cells harbouring expression vectors encoding the TCRs and pharmaceutical compositions comprising the TCRs, nucleic acids or cells of the invention.

The present disclosure relates to mRNA, self-replicating RNA, and temperature-sensitive, self-replicating RNA encoding a cancer antigen. The RNA constructs are suitable for cancer immunotherapy in a mammalian subject, such as a human subject.

The present disclosure provides improved T cell receptors, polynucleotides, polypeptides, vectors, cells, and methods of using the same. Particularly, the present invention relates to T cell receptor-based constructs engineered to comprise one or more additional binding domains, and methods of using the same. In certain embodiments, the one or more binding domains are fused to one or both TCR variable domains. In particular embodiments, the one or more additional binding domains are linked to the TCR with one or more polypeptide linkers.

Disclosed herein are methods for the generation of highly accurate nucleic acid libraries encoding for predetermined variants of a nucleic acid sequence. The nucleic acid sequence may encode for all or part of a TCR or a TCR-binding antigen. The degree of variation may be complete, resulting in a saturated variant library, or less than complete, resulting in a non-saturating library of variants. The variant nucleic acid libraries described herein may designed for further processing by transcription or translation. The variant nucleic acid libraries described herein may be designed to generate variant RNA, DNA and/or protein populations. Further provided herein are method for identifying variant species with increased or decreased activities, with applications in regulating biological functions and the design of therapeutics for treatment or reduction of a disease, such as cancer.

The present invention pertains to antigen recognizing constructs against tumor associated antigens (MAGEA1). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.