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A VIABLE CELL POPULATION, METHOD FOR PRODUCTION AND USES THEREOF
EP3317402
The present disclosure relates to a viable cell population, a method for production and uses thereof. The viable cell population of the present disclosure can be used in medicine, in particular in a method for the treatment of cancer, immune diseases, or viral or bacterial infections. This disclosure may also be suitable for cellular vaccine development. The viable cell population now disclosed has low sialic acid content, is loaded with specific antigens, shows higher antigen presentation, high maturation and co-stimulatory properties, and less tolerogenic properties. The present disclosure relates to a population of viable cells, wherein said population is obtainable by the maturation of the dendritic cells or T2 cells treated with sialidase during 45 min – overnight at 37 °C and, wherein the sialidase concentration vary between 0.002 U/mL - 0.005 U/mL per 1x106 of dendritic cells or T2 cells.
The present disclosure can be applied before or even after phagocytosis of antigen, in contrast to other inventions that can only be applied after antigen upload. This is an advantage that allows maturing DC prior to the antigen upload, thus minimizing the problem of immune suppression posed by tumour antigens that, when given to DC abrogate its maturation (i.e. are tolerogenic). Unexpectedly, in the present disclosure the sialidase treatment does not affect the uptake of tumour antigens, which may be due to the fact that tumour antigens are internalized by several endocytic routes, due to their complex composition. The fact that sialidase treatment does not affect phagocytosis of tumour antigens, presents an advantage compared to other maturation strategies that abrogate antigen internalization and thus have to be performed after upload of antigens. This disclosure thus allows maturing DC prior to the antigen upload, thus minimizing the problem of immune suppression, posed by tolerogenic tumour antigens. [035] Unexpectedly, in the present disclosure the production of IL-10 was reduced in 50% in DC treated with sialidase and uploaded with tumour antigens, compared to untouched DC, suggesting that other signaling pathways are also activated. Decreased IL-10 expression is an advantage since IL-10 is a Th2 cytokine that contributes to immune tolerance. On the other hand, IL-10 stimulates tumour cell proliferation and inhibits cell apoptosis.