Safety Study of Human MUC-1 (Mucin-1) Adenoviral Vector Vaccine for Immunotherapy of Epithelial Cancers
Status:
Unknown status
Trial end date:
2017-06-01
Target enrollment:
Participant gender:
Summary
In epithelial cancer, MUC-1(mucin-1) overexpression is thought to disrupt E-cadherin
function, leading to anchorage-independent tumor cell growth and metastases. Elevated levels
of MUC-1 expression have been found in patients with epithelial cancers of breast, ovarian,
colon and lung. Furthermore, overexpression of MUC-1 is independently correlated with adverse
clinical phenotypes, metastases and resistance to chemotherapy. In animal models, suppressing
the expression of MUC-1 reduces the rates of growth and metastasis and increases the
sensitivity of the cancer to chemotherapy-induced cell death.
In this study, an adenoviral Ad-sig-hMUC-1/ecdCD40L vector encoding a fusion protein in which
the hMUC-1 epithelial antigen is attached to the CD40L (CD40 ligand). The preclinical results
have also shown that two subcutaneous Ad-sig-hMUC-1/ecdCD40L vector injections can induce
immunity through activation of dendritic cells and promotion of antigen specific B cells or
antigen specific CD8 effector T cells which suppresses the growth of hMUC-1 tumor cells in
100% of the vaccinated mice without Interleukin (IL) 2 stimulation being required, this
suggests that the Ad-sig-hMUC-1/ecdCD40L vector prime-hMUC-1/ecdCD40L protein boost has the
potential to be an effective vaccine in epithelial tumors. Therefore, the safety and
tolerability of the Ad-sig-hMUC-1/ecdCD40L vector vaccine will be tested in this phase I
non-randomized open label dose escalation trial for men or women with metastatic or recurrent
epithelial cancers of the lung, breast, ovary, prostate and colon.