CHALLENGES IN GENERATING DC PRODUCTS FOR THERAPY

Regardless of the DC source and culture methods used, therapeutic-grade DCs should meet standard criteria for release. However, no universal criteria for DC release exist, and each laboratory is obliged to define its own release standards based on product sterility, viability, purity, and stability. In the absence of defined universal standards, the quality of DC products is likely to vary between production facilities, and a considerable number of variables must be addressed.^22,23 For example, in addition to the source of DC precursor cells, which may be autologous or allogeneic, the type of tumor antigen(s) used for DC loading, the DC maturation process, their activation state and potency, as well as their ex vivo stability, are among the key variables in the development of DC-based products.

To ensure that a safe and effective DC product will be available for therapy, it is necessary to implement and adhere to SOPs based on experience from preclinical studies and the cumulative current knowledge of DC biology. Endotoxin-free materials are essential for DC production, because even transient exposure of DC precursor monocytes to endotoxin impairs subsequent IL-12 production,²⁴ which seems to be a mandatory factor for effective DC function. Given the variables that are likely to influence the quality of the final product, a central manufacturing site is needed to ensure consistency and quality in processing and in the final product. A facility with HEPA-filtered biological safety cabinets, incubators, centrifuges, cryopreservation devices, and freezers is necessary. The use of components and materials meeting GMP criteria is also required as clinical studies progress from Phase 1 to Phase 3. This type of facility is most likely to meet the challenge of producing a high-quality, optimally functional DC product.