CAR T cells have revolutionized the treatment of relapsed and refractory CD19-positive leukemia and lymphoma. Unfortunately, the majority of patients treated will not achieve durable remissions. Reasons for these suboptimal clinical outcomes can be tied back to intrinsic CAR T cell design and manufacturing processes, factors that are highly amenable to modification and improvement. As CAR T cell therapy is being deployed in spaces outside of CD19-positive disease, these limitations, complications, and setbacks need to be overcome, allowing for the full potential of this novel therapy to be realized. Preclinical work has begun tackling these major roadblocks, paving the way for potentially off-the-shelf products that are safer and more potent. In time, a number of these advances will be translated to the clinic and usher in an era of CARs of the future.
