The development of active specific
immunotherapy depends on the identification of altered
cancer cell-specific molecules or
epitopes that are immunogenic. Many
cancer-specific
peptide or
glycoprotein target
antigens have been identified.
Tumors carrying aberrant
epitopes as a result of underglycosylation of
mucins are associated with poor prognosis in many epithelial
cancers. The aberrant
mucin sialyl-Tn (STn)
epitope, in addition to being a predictor of poor prognosis when expressed in
tumors, is associated with increased aggressiveness and metastatic potential, making it a promising target for
immunotherapy. The STn-
keyhole limpet hemocyanin (KLH)
vaccine (
Theratope) is an investigational active specific
immunotherapy consisting of a synthetic STn
epitope conjugated to a high molecular weight
protein carrier, KLH. The immune response generated by the
STn-KLH vaccine is both humoral and cellular. More than 1000
breast cancer patients with metastatic disease are currently enrolled in a phase III clinical trial to assess the safety and efficacy of the
STn-KLH vaccine. Interim analysis from a current phase III trial has confirmed the safety of the
STn-KLH vaccine, and the clinical outcome awaits the final analysis expected in 2003.