What is the history of chimeric antigen receptors (CARs)?

Three generations of chimeric antigen receptors (CARs) have been developed thus far. First generation CARs were developed in the mid-1980s, and they could only facilitate T cell activation.^1,2 Second generation CARs incorporated co-stimulatory domains to provide both activation and co-stimulation signals, resulting in greater potency. Third generation CARs contain multiple co-stimulatory domains, allowing even more complex signaling and offering potentially even greater potency.¹

References:
1. M. Sadelain, et al., “The basic principles of chimeric antigen receptor design,” Cancer Discov 3(4):388-398, 2013.
2. G. Dotti, et al., “Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T cells,” Immunol Rev 257(1):10, 2014.