ALK.CAR-T

**ALK.CAR-T** is an investigational chimeric antigen receptor (CAR) T-cell therapy engineered to target the anaplastic lymphoma kinase (ALK) receptor, an oncogene overexpressed or mutated in many neuroblastomas and associated with poor prognosis. Developed by Roberto Chiarle's laboratory at Boston Children's Hospital and Harvard Medical School, it demonstrates robust preclinical efficacy against ALK-positive neuroblastoma cell lines, achieving 100% cure rates in mouse models of metastatic disease with ALK amplification. Efficacy is enhanced by pretreatment with ALK inhibitors like lorlatinib, which increase ALK surface expression on tumor cells, including those with low or wild-type ALK, thereby potentiating CAR-T killing without significantly affecting healthy tissues due to ALK's restricted normal expression. A phase 1 clinical trial is planned at Dana-Farber/Boston Children's for relapsed/refractory neuroblastoma, potentially expandable to other ALK-driven cancers like Merkel cell carcinoma.[1][2]