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Clinical development of the STn-KLH vaccine (Theratope)
Nuhad K Ibrahim1, James Lee Murray
1Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030-4009, USA. nibrahim@mdanderson.org
Abstract:
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.
Insights
The investigational sialyl-Tn (STn) vaccine targets aberrant mucin epitopes in cancer. A Phase III trial in metastatic breast cancer patients shows the STn-keyhole limpet hemocyanin (KLH) vaccine is safe, with efficacy results pending.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Aberrant mucin epitopes, such as sialyl-Tn (STn), are linked to poor prognosis and increased metastasis in epithelial cancers.
- These aberrant epitopes represent promising targets for active specific immunotherapy due to their cancer-specific nature.
Purpose of the Study:
- To evaluate the safety and efficacy of the STn-keyhole limpet hemocyanin (KLH) vaccine, an active specific immunotherapy, in patients with metastatic breast cancer.
Main Methods:
- A synthetic STn epitope conjugated to KLH was used to create the STn-KLH vaccine.
- A Phase III clinical trial enrolled over 1000 patients with metastatic breast cancer to assess the vaccine's safety and efficacy.
- The immune response generated by the vaccine was characterized as both humoral and cellular.
Main Results:
- An interim analysis of the Phase III trial confirmed the safety of the STn-KLH vaccine.
- The vaccine elicits both humoral and cellular immune responses.
Conclusions:
- The STn-KLH vaccine is safe for patients with metastatic breast cancer.
- Further analysis is required to determine the vaccine's clinical efficacy, with final results expected in 2003.