Dendritic cell-based vaccines in breast and gynaecologic cancer
ABSTRACT
Major advances in understanding the functional interactions between tumour cells and the host immune system, in particular the generation and regulation of T cell immunity, have revived interest in cancer vaccination strategies. A crucial step for mounting an anti-tumour response is the capture, processing and presentation of tumour antigens (TA) to cognate T cells by professional antigen-presenting cells (APC), followed by their activation and clonal proliferation. Dendritic cells (DC) are potent APC with the unique ability to stimulate primary immune responses. Animal models have demonstrated that TA-charged DC can activate specific cytotoxic T cells (CTL) and even regression of established tumours in cancer-bearing hosts. These findings, as well as the elaboration of methods for generating large numbers of DC ex vivo, have provided a compelling rationale for using DC as potent adjuvants to deliver TA to the immune system in order to trigger or amplify an inadequate response. The capacity of TA-pulsed DC to induce significant CTL immunity translating into occasional therapeutic benefit has been documented in several clinical settings including B cell lymphoma, myeloma, melanoma, prostate, colon, ovarian and renal cell carcinoma. In this review, we summarize key biological functions of DC and focus on recent DC-based vaccination trials of breast, ovarian and cervical cancer.