Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters |
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Authors: | Lotte Engell-Noerregaard Troels Holz Hansen Mads Hald Andersen Per thor Straten Inge Marie Svane |
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Institution: | (1) Department of Oncology, Herlev Hospital, Herlev, Denmark;(2) Department of Hematology, Center for Cancer Immune Therapy (CCIT), Herlev Hospital, Herlev, Denmark |
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Abstract: | During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy
to induce clinically relevant immune responses in patients with malignant diseases. A broad range of cancer types have been
targeted including malignant melanoma which in the disseminated stage have a very poor prognosis and only limited treatment
options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies
on dendritic cell vaccination in melanoma and review different vaccine parameters which are frequently claimed to have a possible
influence on clinical response. These parameters include performance status, type of antigen, DC maturation status, route
of vaccine administration, use of adjuvant, and vaccine induced immune response. In total, 38 articles found through Medline
search, have been included for analysis covering a total of 626 patients with malignant melanoma treated with DC based therapy.
Clinical response (CR, PR and SD) were found to be significantly correlated with the use of peptide antigens (p = 0.03), the use of any helper antigen/adjuvant (p = 0.002), and induction of antigen specific T cells (p = 0.0004). No significant correlations between objective response (CR and PR) and the tested parameters were found. However,
a few non-significant trends were demonstrated; these included an association between objective response and use of immature
DCs (p = 0.08), use of adjuvant (p = 0.09), and use of autologous antigen preparation (p = 0.12). The categorisation of SD in the response group is debatable. Nevertheless, when the SD group were analysed separately
we found that SD was significantly associated with use of peptide antigens (p = 0.0004), use of adjuvant (p = 0.01), and induction of antigen specific T cells (p = 0.0003). No specific route of vaccine administration showed superiority. Important lessons can be learned from previous
studies, interpretation of these findings should, however, be done with reservation for the many minor deviations in the different
treatment schedules among the published studies, which were not considered in order to be able to process and group the data. |
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Keywords: | Cancer Dendritic cells Malignant melanoma Immunotherapy Tumour vaccines |
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