Transimmunization and the evolution of extracorporeal photochemotherapy.
We are now aware that extracorporeal photopheresis (ECP) - in which a patient's leukocytes are isolated, passed through an ultrathin clear plastic plate, and exposed to 8-methoxypsoralen (8-MOP) and ultraviolet A light prior to reinfusion - is a simple and efficient dendritic cell (DC) therapy and the first FDA approved selective immunotherapy for cancer. DCs, as the most effective antigen presenting cells (APCs), are central to many ongoing efforts to stimulate immune responses to cancer cells. Moreover, ECP has not only demonstrated efficacy in the treatment of a T cell malignancy--namely cutaneous T-cell lymphoma (CTCL)--but also in treatment of oligoclonal T-cell-mediated diseases such as graft-versus-host-disease (GVHD) and organ transplant rejection. Recent advances in the understanding of DC/T-cell interactions provide insight into how ECP-induced DCs (EI-DCs) can be utilized to stimulate specific T-cell (i.e. anti-tumor) responses, or down-regulate a pre-existing potent T-cell response. The mechanism of this apparent paradox of EI-DC functionality is likely dependent on several fundamental principles: (1) the status of existing in vivo T-cell reactions, (2) the temporal stage of EI-DC differentiation, and (3) the affinity of the available repertoire of T-cell receptors (TCRs) for the antigen(s) in question. Further investigation into DC/T-cell interactions will help to shape the future of ECP and the ability to optimize this therapy for the desired immune effect. To this end, we are developing and testing Transimmunization to replace conventional ECP.
michael.girardi@yale.edu
Michael
M
Girardi
Jeffrey
J
Schechner
Earl
E
Glusac
Carole
C
Berger
Richard
R
Edelson
D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006086:Graft vs Host Disease / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000628:therapy; D017893:Photopheresis / Q000379:methods* / Q000639:trends; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology