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

• Published in: British journal of cancer 2010-10, Vol.103 (9), p.1415-1421
• Main Authors: Lesterhuis, W J, de Vries, I J M, Aarntzen, E A, de Boer, A, Scharenborg, N M, van de Rakt, M, van Spronsen, D-J, Preijers, F W, Figdor, C G, Adema, G J, Punt, C J A
• Format: Article
• Language: English
• Subjects: 631/250/2504/133; 692/699/67/1059/99; 692/699/67/1504/1885/1393; 692/700/565/251/1567; Adjuvants; Aged; Antibody Formation; Antigens; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-Lymphocytes - immunology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cancer Research; Cancer Vaccines - administration & dosage; Capecitabine; Carcinoembryonic antigen; Cell death; Chemotherapy; Chemotherapy, Adjuvant; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - immunology; Colorectal cancer; Cytotoxicity; Data processing; Dendritic cells; Dendritic Cells - immunology; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Drug Resistance; Epidemiology; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hypersensitivity (delayed); Hypersensitivity, Delayed - etiology; Immune system; Immunogenicity; Immunotherapy; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical research; Medical sciences; Middle Aged; Molecular Medicine; Oncology; Organoplatinum Compounds - administration & dosage; oxaliplatin; Peptides; Pilot Projects; Skin tests; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-Lymphocytes - immunology; Translational Therapeutics; Tumors; Vaccination; Vaccines
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605935

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.