The purpose of this report is to describe efforts to understand the immune mechanism of action that resulted in a complete response in a patient with progressive, refractory, metastatic melanoma after treatment with a therapeutic vaccine consisting of autologous dendritic cells loaded with autologous tumour antigens derived from self-renewing cells in cell culture. Her HLA type was determined to be HLA B27, with significant alterations in the HLA-A region. When compared to her leukocytes, an exomic examination of growing tumour cells revealed over 2800 non-synonymous mutations. The histology of resected tumour lesions revealed no indication of an active or suppressed immune response.
Cryopreserved blood samples collected at week-0, one week before the first of three three-weekly vaccination injections, and week-4, one week after the third dose, were examined using a protein array and compared for 110 distinct serum indicators. She showed significant increases of amyloid A, IL-12p40, IL21, IL-22, IL-10, IL-16, GROa, TNF-alpha, IL-3, and IL-2 at baseline, as well as a smaller elevation of IL-15. One week after receiving three weekly vaccines, she experienced an additional 80% rise in amyloid A, a 66 percent increase in IL-22, a 92 percent drop in IL12p40, a 45 percent decrease in TGF-, and a 26 percent decrease in IL-10. The findings showed that three weeks following the initial DCV injection, vaccine-induced alterations in this patient were most consistent with increased innate and Th1 immune responses rather than Th2 or Th17.
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