Ad-sig-hMUC-1/ecdCD40L vaccine(ClinDatrix)

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.