Human
mucin MUC1 is abundantly expressed in some
cancers of epithelia] origin and is largely restricted to the apical surface of secretory cells in normal tissues. It is, therefore, a potential target for
cancer immunotherapy. In preparation for clinical trials,
vaccines containing synthetic MUC1
peptides of different lengths and sequences mixed with various adjuvants or covalently attached, using different linker methods, to
protein carrier keyhole limpet hemocyanin (KLH) were studied in mice. MUC1
peptides (containing 30
amino acids), plus adjuvants
QS-21 or Bacillus Calmette-Guerin, were incapable of inducing antibody. However, MUC1
peptides conjugated to KLH (MUCl-KLH), plus
QS-21, induced high titer antibody against the immunizing
peptides and against MUC1-expressing
tumor cells. Although T-cell responses, including delayed-type
hypersensitivity, lymphocyte proliferation, and CTL, were not observed in mice immunized with these
vaccines, significant protection from MUC1-expressing
tumor cell challenge in mice immunized with MUC1-KLH was observed. Based on these studies, a
vaccine containing MUC1-KLH conjugate prepared with m-maleimidobenzoyl-
N-hydroxysuccinimide ester linker, plus
QS-21, has been constructed for testing in clinical trials.