Vaccination of breast cancer patients with MUC1 keyhole limpet hemocyanin conjugate plus QS-21

Excerpt

Immunotherapeutic approaches to the management of solid tumours have been an area of active research in recent years. Approaches have been particularly advanced for melanoma, for which a number of distinct tumour antigens have been identified. A number of differentiation antigens have also been identified on breast cancer cells. One of these is MUC1, which is a transmembrane glycoprotein. MUC1 has been identified on a number of different tumour types a variety of normal epithelial cells. There are differences in MUC1 expression, with greater exposure of MUC1 epitopes to the immune system in tumours due to altered tissue structure leading to MUC1 expression on multiple cell surfaces, and also due to changed structure with abnormal glycosylation. Cloning and sequencing of MUC1 has led to the development of various synthetic peptides for use in vaccines. These peptides elicit both humoral and cellular immune responses in animal models. The lack of development of intrinsic immune responses against endogenous MUC1 on tumour cells suggests that there is low tumour immunogenicity. This may be overcome by conjugating the MUC1 peptide with a protein carrier and with an immune adjuvant. Keyhole limpet hemocyanin (KLH) is one such protein carrier obtained from the blood of the keyhole limpet, and QS-21 is an immune adjuvant obtained from the bark of a South American tree. This combination of KLH and QS-21 has been shown to be effective in inducing antibody responses. …