Fred Hutchinson Cancer Research Center Seattle United States
In this reporting period, we have generated and validated lentiviral constructs in anticipation of studies evaluating the cooperation of MYCN overexpression with TP53 and RB1loss in the initiation of neuroendocrine prostate cancer NEPC. We have continued validating candidate NEPC cell surface antigens arising from integrated transcriptome and cell surface proteome analysis of prostate cancer cell lines. CEACAM5 carcinoembryonic antigen related cell adhesion molecule 5 was previously characterized as a cell surface marker enriched in NEPC. We also identified L1CAM L1 cell adhesion molecule and validation of L1CAM expression in patient-derived xenograft and archived clinical NEPC biospecimens is ongoing. In the next phase of our studies, we are evaluating a clinical-grade CEACAM5 antibody-drug conjugate in preclinical CEACAM5-postive NEPC models. In addition, we will start the process of humanizing an available chimeric mousehuman antibody targeting L1CAM that has shown preclinical therapeutic activity in various L1CAM-expressing cancer models.