Adoptive cellular therapy (ACT) is now considered a bona fide treatment modality within the evolving field of anticancer immunotherapy. Great advances have enabled the adoptive transfer of tumour-selective lymphocytes for the treatment of a variety of malignancies. Unfortunately, this selectivity has led to the emergence of antigen-loss variants. New strategies need to be employed to minimize the incidence of this phenomenon, enabling the full potential of ACT to be realized.