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Approaches to Dendritic Cell‐Based Immunotherapy after Peripheral Blood Stem Cell Transplantation

Abstract: High‐Dose chemotherapy with peripheral blood progenitor cell transplantation (PBPCT) is a potentially curative treatment option for patients with both hematological malignancies and solid tumors, including breast cancer. However, based on a number of clinical studies, there is strong evidence that minimal residual disease (MRD) persists after high‐dose chemotherapy in a number of patients, which eventually results in disease recurrence. Therefore, several approaches to the treatment of mrd are currently being evaluated, including treatment with dendritic cell (DC)‐based cancer vaccines. DCs, which play a crucial role with regard to the initiation of T‐lymphocyte responses, can be generated ex vivo either from CD34+ hematopoietic progenitor cells or from blood monocytes. They can be pulsed in vitro with tumor‐derived peptides or proteins, and then used as a professional antigen‐presenting cell (APC) vaccine for the induction of antigen‐specific T‐lymphocytes in vivo. This paper summarizes our preclinical studies on the induction of primary HER‐2/neu specific cytotoxic T‐lymphocyte (CTL) responses using peptide‐pulsed DC. As HER‐2/neu is overexpressed on 30‐40% of breast and ovarian cancer cells, this novel vaccination approach might be particularly applicable to advanced breast or ovarian cancer patients after high‐dose chemotherapy and autologous PBPCT.