Although evidence has long supported that the third-generation CARs, which integrate two co-stimulatory domains of CD28 and 41BB, can increase the capacity of T cell expansion and persistence for potentially better clinical depth (CR) breath (RR) and durability (PFS or OS), eighty percent of CAR clinical trials by far use second-generation co-stimulatory domains of either 41BB or CD28. The key technical challenge hindering the clinical adoption of third-generation CARs has been the abnormally low expression of chimeric proteins. Neomics has made a breakthrough in designing the third-generation chimeric proteins with high-expression levels equivalent to the widely used second-generation chimeric proteins. T cells expressing third-generation chimeric proteins manifest enhanced immune function. The proprietary third-generation platform has a potential to bring a fundamental change to the development of T cell products. By replacing with different extracellular domains targeting various proven, validated, or novel targets from hematology and solid tumors, the success of the third-generation CAR platform will lay the foundation for a newer generation of CAR T and TCR T pipeline with a clear edge on clinical efficacy.