Reduction of liver metastases outgrowth by tumour antigen-pulsed dendritic cell vaccination

Abstract

Over 50% of patients diagnosed for primary colorectal carcinoma develop liver metastases. Partial liver resection is the single effective treatment improving dismal survival [1]. Since few patients, however, are candidates for resection, development of therapies that prevent formation of liver metastases is warranted. Outgrowth of metastases may be reduced or prevented by the action of tumour specific T cells, which are activated in T cell areas of lymph nodes by professional antigen presenting cells (APC). Dendritic cells (DC) are the most potent APC, capable of providing the necessary co-stimulatory signals [2]. DC have been derived in vitro from blood monocytes (moDC) for use in clinical trials to generate tumour specific immune responses, and results of vaccination studies in melanoma patients are encouraging [3,4]. However, vaccination for various other cancer types and treatment of established metastases with antigen-pulsed DC has been disappointing. In the present study we investigated whether vaccination of rats with tumour antigen-pulsed moDC could prevent outgrowth of experimental liver metastases originating from colorectal cancer. Additionally, the therapeutic effect of moDC on existing micrometastases was evaluated.