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flipper44

04/19/16 7:42 PM

#59334 RE: Doc logic #59333

Yes. One way for DCs to survive a hypoxic environment at the subdermal injection site is to make each separate injection dose smaller but increase the number of injections. For instance, the phase III DCVax-L trial decreased the amount of DCs per injection but doubled the number of injections per administration. Another way is to add an adjuvant like poly-iclc.

Whereas when injected intratumorally, il-12 secretion by the dendritic cell can ultimately increase DC migration, and I would imagine they also reduce the amount per injection while increasing the number of injections per administration. With Direct they even developed a special needle angled at around 60 degrees that they could turn and make multiple injections without having to reposition the entire syringe.

On your other point, the maturation and activation process with DCVax-Direct (during manufacturing) appears to exhibit control over the ultimate secretion production/quantity capacity of dendritic cells for each preferred cytokine. I think we are still waiting to find out whether this is more determined by patient dendritic cell natural capacity, or perhaps instead might be achieved for all patients' selected dendritic cells during the manufacturing process. (IMHO.)