Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising an AFP peptide and an MHC class I protein. Also provided are methods of making and using these constructs.

The neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis including the unmutated peptide QYNPIRTTF (SEQ ID NO: 1) discovered on HLA-A*24:02 which is derived from the neuroblastoma dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, peptide-centric chimeric antigen receptors (PC-CARs) were developed via a counter panning strategy using predicted potentially cross-reactive peptides. Informed by computational modeling, PHOX2B peptide centric CARs were demonstrated to also recognize QYNPIRTTF (SEQ ID NO: 1) presented by HLA-A*23:01 and the highly divergent HLA-B*14:02. Potent and specific killing of neuroblastoma cells expressing these HEAs in vitro was shown along with complete tumor regression in mice.

The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising an AFP peptide and an MHC class I protein. Also provided are methods of making and using these constructs.

The invention relates to the field of cancer immunotherapy by employing CD4+ cell populations, CD8+ cell populations, or a combination thereof, comprising bicistronic inhibitory chimeric antigen receptor (iCAR)/activating chimeric antigen receptor (aCAR) constructs for use in cancer treatment therapies.

The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising an AFP peptide and an MHC class I protein. Also provided are methods of making and using these constructs.

This invention provides an isolated or purified T-cell receptor (TCR) having antigenic specificity for the mutated human p53R175H. The inventive TCR can recognize the HLA-A2 restricted mutant p53R175H peptide (HMTEVVRHC) but cannot recognize the wild-type p53R175 peptide (HMTEVVRRC). The inventive TCR can also be activated by tumor cells harboring a mutated human p53R175H in the context of HLA-A2. The invention further provides related polypeptides, proteins, nucleic acids, recombinant expression vectors, host cells, populations of cells and pharmaceutical compositions relating to the TCR of the invention. Methods of treating or preventing cancer in a mammal are further provided by the invention.