Back to Search
Start Over
An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2010 Sep; Vol. 120 (9), pp. 3234-41. Date of Electronic Publication: 2010 Aug 02. - Publication Year :
- 2010
-
Abstract
- Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.
- Subjects :
- Adult
Aged
Alphavirus immunology
Antibody-Dependent Cell Cytotoxicity genetics
Antibody-Dependent Cell Cytotoxicity immunology
Antigens, Neoplasm genetics
Antigens, Neoplasm immunology
Carcinoembryonic Antigen genetics
Carcinoembryonic Antigen immunology
Colorectal Neoplasms genetics
Colorectal Neoplasms immunology
Colorectal Neoplasms pathology
Female
Humans
Male
Middle Aged
Neoplasms genetics
Replicon
Alphavirus genetics
Antibodies, Neutralizing
Genetic Vectors
Neoplasms immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 120
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 20679728
- Full Text :
- https://doi.org/10.1172/JCI42672