Nature: Philadelphia Children's Hospital has developed a new CAR T cell therapy

Researchers at the Children's Hospital of Philadelphia have recently developed a new cancer immunotherapy to treat aggressive neuroblastoma

Using large data sets and advanced calculation methods, researchers can identify specific peptides that exist on the surface of tumor cells and use a new "peptide-centric" chimeric antigen receptor (PC-CAR) Targeted therapy

Cancer immunotherapy based on CAR T cells is a breakthrough for hematological tumors, but this approach has not made significant progress in the treatment of solid tumors, partly because of the lack of tumor-specific targets

However, fragments of these proteins may appear on the surface of tumor cells through the presentation of peptides of the major histocompatibility complex (MHC).

Neuroblastoma is an aggressive childhood cancer that has almost no mutations, but is driven by an epigenetic dysregulated transcription network

Despite these problems, researchers at the Children's Hospital of Philadelphia hypothesized that some peptides on the cell surface of neuroblastoma are derived from proteins that are essential for tumor growth and survival and can be targeted by synthetic CARs

To this end, the researchers isolated MHC molecules from neuroblastoma cells and determined which peptides were present and at what abundance

They prefer to select peptides derived from tumor-essential genes that can participate in the immune response

Using this multi-omics method, the researchers identified an unmutated peptide QYNPIRTTF, which is derived from neuroblastoma-dependent genes and transcriptional regulator PHOX2B

Through cooperation with the antibody development company Myrio Therapeutics, researchers have developed PC-CARs for this peptide and showed that these PC-CARs can recognize tumor-specific peptides on different types of HLA, which means that this therapy can be applied to Patients of different genetic pedigrees

In follow-up studies, they found that this PC-CAR can specifically kill neuroblastoma cells expressing these HLAs in vitro

Corresponding author, Dr.

Dr.

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Yarmarkovich, M.