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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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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