Selective immmunotherapy through extracorporeal photochemotherapy: yesterday, today, and tomorrow

Since the first patient was treated with extracorporeal photo chemotherapy (ECP) in 1978, more than 150 ECP centers have emerged worldwide to deliver more than 200,000 ECP treatments to patients who have cutaneous T-cell lymphoma (CTCL) and other T-cell-mediated disorders. In 1988, ECP became the first selective immunotherapy to be approved by the United States Food and Drug Administration (USFDA) for any type of cancer. The following decade would reveal that even as a monotherapy, ECP could result in complete remission of a T-cell lymphoma, without the toxicity and risks that were associated with traditional chemotherapeutic approaches. During the 1990s, investigators applied ECP in various clinical trials and moved this technology forward by identifying patients who were most likely to respond, combined it with other therapies for CTCL, and used it in autoimmune diseases and alloreactive processes, such as graft-versus-host disease (GVHD) and organ transplant rejection. The science to elucidate the mechanisms of ECP's activity has lagged, largely awaiting the advancement of our understanding of 8-methoxypsoralen induction of apoptosis, class I major histocompatibility complex presentation of tumor antigens, and dendritic antigen-presenting cell (DC) biology. Although much remains to be learned, we appreciate that ECP simultaneously and efficiently induces apoptosis of disease-causing T cells and large-scale conversion of monocytes to functional DC. By processing and presenting the unique antigenic determinants of malignant T-cell clones, the DC can initiate a clinically relevant anti-CTCL cytotoxic response (Fig. 1). This article reviews clinical trials of ECP in CTCL (referring principally to the mycosis fungoides and Sezary syndrome variant [SS]), the evolving scientific understanding of ECP's mechanisms of action, and possible future directions for ECP.