Immunotherapy of Breast Cancer Using Novel Her2/neu-Based Vaccines
Abstract
NY-ESO-1 is expressed in 40% of malignant breast tumors and is a promising antigen for breast cancer immunotherapy. Recombinant Listeria monocytogenes expressing specific target antigens is a highly effective vaccine vector, inducing cell-mediated immunity capable of regressing established tumors. The full-length and partial sequences (residues 1-108, 101- 156 and 148-180) of NY-ESO-1 were cloned as fusion genes with listeriolysin-O (LLO) and expressed in Listeria. Secretion of the fusion proteins from constructs containing the hydrophobic C-term region of NY-ESO-1 was poor or absent. Vaccination of mice with Listeria expressing either the full-length NY-ESO-1 or its fragments did not significantly impact tumor growth of the mammary carcinoma 4T1 cell line, which was engineered to express NY-ESO-1. We observed that these Listeria constructs were deficient in intracellular proliferation in murine J774 cells, and are highly attenuated in mice. New constructs were made, fusing NY-ESO-1 to the LLO PEST sequence only, which is an immunologically important domain in LLO. The PEST-NY-ESO-1 constructs showed a better proliferation in J774 cells between B and 24 hours. We are also trying to express NY-ESO-1 under the control of the listerial actA promoter, which is activated in the cytosol of the infected cell. These new constructs are currently being tested in animal studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436909
Entities
People
- Ivonne Paterson
- Paulo Maciag
Organizations
- University of Pennsylvania