St. Jude Reference #SJ-18-0043
Description
CAR-T therapy is an increasingly popular way to target and kill cancer cells. The efficacy of CAR-T cell therapy relies heavily on the identification of an antigen that has an appreciable degree of expression and is relatively tumor-specific. Researchers at St. Jude describe a method to transform heterogeneous RNA expression data in order to make meaningful comparisons across distinct data cohorts, sequencing protocols, and instruments.
They created a CAR-T prediction algorithm to assess a tumor-specific set of CAR-T targets utilizing gene localization, transformed RNA expression values, and relative protein expression. The methodology is extrapolated to predict effective CAR-T targets in pediatric Acute Myeloid Leukemia tumors of M7 subtype, given patient prognoses are poor.
Protease Serine 21 (PRSS21), also known as testisin, was identified as an antigen preferentially expressed on the cell surface of AML cells, but not normal hematopoietic stem cells or mature neutrophils, which makes it a target for CAR-T or other forms of immunotherapies for AML, leukemias and solid tumors. This is a major advantage in comparison to antigens that are currently being explored as immunotherapeutic targets (e.g. CLL1: expressed on all mature neutrophils; CD33 and CD123 expressed on bone marrow stem cells).
Keywords
Immunology, data heterogeneity, CAR-T cell therapy, bioinformatics, acute myeloid leukemia, AML, solid tumors Protease Serine 21 (PRSS21), testisin.
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