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. 2010 Oct 26;103(9):1415-21.
doi: 10.1038/sj.bjc.6605935. Epub 2010 Oct 5.

A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients

W J Lesterhuis  1 , I J M de Vries, E A Aarntzen, A de Boer, N M Scharenborg, M van de Rakt, D-J van Spronsen, F W Preijers, C G Figdor, G J Adema, C J A Punt
Affiliations

A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients

W J Lesterhuis et al. Br J Cancer. .

Abstract

Background: Dendritic cell (DC) vaccination has been shown to induce anti-tumour immune responses in cancer patients, but so far its clinical efficacy is limited. Recent evidence supports an immunogenic effect of cytotoxic chemotherapy. Pre-clinical data indicate that the combination of chemotherapy and immunotherapy may result in an enhanced anti-cancer activity. Most studies have focused on the immunogenic aspect of chemotherapy-induced cell death, but only few studies have investigated the effect of chemotherapeutic agents on the effector lymphocytes of the immune system.

Methods: Here we investigated the effect of treatment with oxaliplatin and capecitabine on non-specific and specific DC vaccine-induced adaptive immune responses. Stage III colon cancer patients receiving standard adjuvant oxaliplatin/capecitabine chemotherapy were vaccinated at the same time with keyhole limpet haemocyanin (KLH) and carcinoembryonic antigen (CEA)-peptide pulsed DCs.

Results: In 4 out of 7 patients, functional CEA-specific T-cell responses were found at delayed type hypersensitivity (DTH) skin testing. In addition, we observed an enhanced non-specific T-cell reactivity upon oxaliplatin administration. KLH-specific T-cell responses remained unaffected by the chemotherapy, whereas B-cell responses were diminished.

Conclusion: The results strongly support further testing of the combined use of specific anti-tumour vaccination with oxaliplatin-based chemotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Treatment schedule.
Figure 2
Figure 2
Frequencies of PBMC subsets during treatment with oxaliplatin/capecitabine and DC vaccination. Means with s.d. are depicted. (A) Total T cells (CD3+). (B) T helper cells (CD4+). (C) Cytotoxic T cells (CD8+). (D) Natural killer cells (CD3-/CD56+). (E) Monocytes (CD14+). (F) B cells (CD19+).
Figure 3
Figure 3
(A) Proliferative non-specific T-cell response upon PHA-stimulation during treatment with oxaliplatin/capecitabine and DC vaccination. In all patients, an increase in proliferation was observed during treatment. (B) Also the IFN-γ production upon PHA-stimulation increased during treatment (data of four tested patients are given; the means with s.d. are depicted).
Figure 4
Figure 4
All patients showed a proliferative CD4+ T-cell response against the control antigen KLH. (A) A representative patient (patient 7) is shown. (B) However, B-cell responses against KLH upon vaccination could not be detected in 6 out of 7 patients.
Figure 5
Figure 5
In four out of seven patients, CEA-specific DTH-infiltrating T cells were observed after completion of vaccination, either by (A) tetramer staining or (B) IFN-γ and IL-2 release upon co-culture with CEA-loaded target cells. Data from a representative patient (no. 2) are shown.
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