Durable complete clinical responses in a phase I/II trial using an autologous XXXX cell/dendritic cell vaccine.

@entity1 @entity404 @entity66 @entity5 @entity56 @entity74 @entity320
Advanced @entity320 is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides as the source of antigens, and rely on foreign proteins as a source of help to generate a cell-mediated immune response. This approach limits @entity1 accrual, because currently defined, non-mutated epitopes are restricted by a small number of human leucocyte antigens. It also fails to take advantage of mutated epitopes peculiar to the @entity1 's own @entity5 , and of @entity404 + T lymphocytes as potential effectors of anti- @entity5 immunity. We therefore sought to determine whether a fully autologous DC vaccine is feasible, and of therapeutic benefit. @entity1 with American Joint @entity5 Committee stage IV @entity320 were treated with a fully autologous immunotherapy consisting of monocyte-derived DC, matured after culture with irradiated @entity5 cells. Of 19 @entity1 enrolled into the trial, sufficient @entity5 was available to make treatments for 17. Of these, 12 received a complete priming phase of six cycles of either 0.9x10(6) or 5x10(6) DC/intradermal injection, at 2-weekly intervals. Where possible, treatment continued with the lower dose at 6-weekly intervals. The remaining five @entity1 could not complete priming, due to @entity74 . Three of the 12 @entity1 who completed priming have durable complete responses (average duration 35 months+), three had partial responses, and the remaining six had @entity74 (WHO criteria). Disease regression was not correlated with dose or with the development of delayed type @entity56 responses to intradermal challenge with irradiated, @entity5 . However, plasma S-100B levels prior to the commencement of treatment correlated with objective clinical response ( P=0.05) and survival (log rank P<0.001). The treatment had minimal side-effects and was well tolerated by all @entity1 . Mature, monocyte-derived DC preparations exposed to appropriate @entity5 antigen sources can be reliably produced for @entity1 with advanced @entity320 , and in a subset of those @entity1 with lower @entity66 their repeated administration results in durable complete responses.
