Correlation of clinical outcome with natural killer (NK) response to an anti-cancer, dendritic cell-based vaccine.
2585 Background: Cancer vaccines have generally been developed to activate antigen-specific T cell responses, but few studies have attempted to evaluate the non-specific, yet potentially clinically-relevant, NK response to immunization. We hypothesized that the NK response would predict clinical benefit in immunized patients.In a phase I clinical trial of a vaccine consisting of autologous dendritic cell (DC) loaded with a fowlpox vector encoding CEA (rF-CEA(6D)-TRICOM, we measured CEA-specific immune responses by ELISPOT assay and reported increases in 12/14 patients (Proc ASCO2004, abst 2508). Using archived peripheral blood specimens (n=9) from before and after all immunizations, we measured CD3-CD56+ NK% and NK cytolytic activity against the NK target K562. These data were compared with the clinical outcome of the patients.There were no differences in the percentage of NK cells or NK markers NKG2A, NKG2C, NKG2D before or after immunization. In contrast, NK cytolytic activity increased in 4 patients (range 2.5 to 5 times greater lytic activity), was stable in 2 and decreased in 3. When patients were grouped by clinical activity (stable disease/no evidence of disease (n=5) versus progressive disease (N=4) at three months), we observed that the majority of those with stable disease/no evidence of disease had increases in their NK activity (Chi Square, P= 0.0163). The NK results predicted more closely the clinical outcome than did T cell responses (Chi Square, P=NS).NK responses following immunization with a dendritic cell vaccine are associated with clinical benefit as indicated by a lack of progressive disease. Monitoring of NK response during vaccine studies should be routinely performed. No significant financial relationships to disclose.
Morse, M; Osada, T; Hobeika, A; Chui, S; Clay, T; Lyerly, HK
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