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 spectrum of the tumor's distinctive antigens, without requiring their prior identification. Toward these goals, we describe a modification of standard extracorporeal photopheresis (ECP) which initiates, within a single day, both monocyte-to-dendritic cell (DC) differentiation and malignant cell apoptosis. The transition of monocytes to immature DCs was identified by the expression of cytoplasmic CD83 and membrane CD36 in the absence of membrane CD14 staining, as well as induction of membrane CD83 expression. Differentiating DCs were avidly phagocytic and engulfed apoptotic malignant T cells. Differentiating DCs were capable of stimulating significant proliferation of normal alloreactive lymphocyte responders, indicting increased expression of membrane MHC class II molecules. This approach provides a clinically practical means of developing tumor-loaded cells that have initiated the transition to DCs without the requirement of exogenous cytokines, excessive cellular manipulation or isolation. Construction of DC vaccines using this methodology can be generalized to other diseases and may offer a novel approach for improved cancer immunotherapy.
Department of Dermatology, Yale University, School of Medicine, 333 Cedar Street, New Haven, CT 65520-8059, USA. Carole.Berger@Yale.edu
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CL
Berger
A L
AL
Xu
D
D
Hanlon
C
C
Lee
J
J
Schechner
E
E
Glusac
I
I
Christensen
E
E
Snyder
V
V
Holloway
R
R
Tigelaar
R L
RL
Edelson
D015703:Antigens, CD; D017209:Apoptosis; D018955:CD36 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D007937:Leukapheresis; D007962:Leukocytes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000378:metabolism; D010587:Phagocytosis; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D000097802:CD83 Antigen
D015703:Antigens, CD; D018955:CD36 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen