Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic. Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR. By engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction. This is a promising new therapeutic approach known as adoptive cell therapy.
Anaplastic lymphoma kinase (ALK, CD246) is a tumor-associated antigen that is expressed on the cell surface of pediatric neuroblastomas and some non-small cell lung carcinomas (NSCLC). This technology from NCI's Pediatric Oncology Branch concerns the development of four (4) CARs, each comprising a different antibody binding fragment to ALK. The CARs, known individually as ALKCAR15, ALKCAR48, ALKCAR53 and ALKCAR58, can be used in adoptive cell therapy treatment for neuroblastoma and other solid tumors which overexpress ALK or variants thereof.
- Treatment of cancers associated with expression of ALK or variants thereof; Specific cancers include neuroblastoma, NSCLC and other solid tumors
- High affinity of the ALKCAR15, ALKCAR48, ALKCAR53 and ALKCAR58 increases the likelihood of successful targeting;
- Targeted therapy decreases non-specific kiling of healthy, essential cells, resulting in fewer non-specific side-efects and healthier patients
Rimas J. Orentas, Crystal L. Mackall
Orentas RJ, et al. ALK (anaplastic lymphoma kinase, CD246) specific CARs: new immunotherapeutic agents for the treatment of pediatric solid tumors. [DOI 10.1186/2051-1426-1-S1-P27]
- U.S. Patent Filed: U.S. Patent Application Number 61/865,845, Filed 06 Nov 2013