Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products.
Dendritic cell (DC) active immunotherapy is potentially efficacious in a broad array of malignant disease settings. However, challenges remain in optimizing DC-based therapy for maximum clinical efficacy within manufacturing processes that permit quality control and scale-up of consistent products. In this review we discuss the critical issues that must be addressed in order to optimize DC-based product design and manufacture, and highlight the DC based platforms currently addressing these issues. Variables in DC-based product design include the type of antigenic payload used, DC maturation steps and activation processes, and functional assays. Issues to consider in development include: (a) minimizing the invasiveness of patient biological material collection; (b) minimizing handling and manipulations of tissue at the clinical site; (c) centralized product manufacturing and standardized processing and capacity for commercial-scale production; (d) rapid product release turnaround time; (e) the ability to manufacture sufficient product from limited starting material; and (f) standardized release criteria for DC phenotype and function. Improvements in the design and manufacture of DC products have resulted in a handful of promising leads currently in clinical development.
Nicolette
C A
CA
Argos Therapeutics, 4233 Technology Drive, Durham, NC, United States.
Healey
D
D
Tcherepanova
I
I
Whelton
P
P
Monesmith
T
T
Coombs
L
L
Finke
L H
LH
Whiteside
T
T
Miesowicz
F
F
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D002454:Cell Differentiation; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D014611:Vaccination / Q000379:methods*
D019496:Cancer Vaccines