The Clone Ranger?

Abstract

A recent article describing a T-lymphocyte cell clone that eliminated melanoma in a patient with advanced metastatic disease1 excited an exceptionally high level of publicity worldwide. An accompanying Perspective in the New England Journal of Medicine breathlessly concluded that for cell therapy of cancer, “the endgame has begun.”2 Such broad enthusiasm for an article on a T-cell clone seems largely based on a hoped-for analogy to the development of monoclonal antibodies, which clearly opened a new era in immunotherapy. This may be an unwise comparison. Eradication of melanoma using a single T-lymphocyte clone is indeed of considerable interest and value, but as Cassian Yee (the report's senior author) himself points out, we need to be careful about assuming broader benefits for the approach.3 In practical terms, cloned T cells of the desired specificities and phenotype are hard to consistently manufacture in large numbers, whereas biologically, the T-cell component of the immune system is designed to operate as a phenotypically and functionally diverse cellular network, and an individual clone may only rarely possess all the necessary characteristics for safe and effective activity.