Induction of human tumor-loaded dendritic cells

A preferred anti-cancer vaccine would be tumor-specific, simple to rapidly construct and safe to administer. It would permit immunization against a sp ectrum of the tumor's distinctive antigens, without requiring their prior i dentification. Toward these goals, we describe a modification of standard e xtracorporeal photopheresis (ECP) which initiates, within a single day, bot h monocyte-to-dendritic cell (DC) differentiation and malignant cell apopto sis. The transition of monocytes to immature DCs was identified by the expr ession of cytoplasmic CD83 and membrane CD36 in the absence of membrane CD1 4 staining, as well as induction of membrane CD83 expression. Differentiati ng DCs were avidly phagocytic and engulfed apoptotic malignant T cells. Dif ferentiating DCs were capable of stimulating significant proliferation of n ormal alloreactive lymphocyte responders, indicting increased expression of membrane MHC class II molecules. This approach provides a clinically pract ical means of developing tumor-loaded cells that have initiated the transit ion to DCs without the requirement of exogenous cytokines, excessive cellul ar manipulation or isolation. Construction of DC vaccines using this method ology can be generalized to other diseases and may offer a novel approach f or improved cancer immunotherapy. (C) 2001 Wiley-Liss, Inc.