Vaccine development for oral carcinoma is the current major research objective of my laboratory. The long-term objective is to develop a vaccine that can be used in the overall management of patients with squamous cell carcinoma of the head and neck (SCCHN). The vaccination strategy combines known requirements for generation of a robust anti tumor immune response--antigen presentation, allogeneic stimulation and the secretion of immune-augmenting cytokines. The vaccine is prepared by transfer of DNA from squamous carcinoma cells into a highly immunogenic syngeneic/allogeneic cell line in which genes specifying tumor associated antigens (TAAs) are expressed. The recipient cells are modified in advance of DNA-transfer to secrete cytokines. This type of vaccine is based on the principle that TAAs are the products of mutant and dysregulated genes in cancer cells and that transfer of tumor-DNA into recipient cells results in stable integration and long-term expression of the genes specifying TAAs. Prior published data in mice indicate that immunization with transfected cells induced strong anti tumor immune responses, immunological memory and prolongation of survival. Our recent studies (PNAS, 99: 9415-9420, 2002) confirm the immunogenic properties of recipient cells transfected with DNA from human oral carcinomas. This type of vaccine has a number of advantages, including the selection of immunogenic recipient cells, in which the transferred DNA is replicated. Thus, the vaccine can be prepared with DNA derived from small amounts of tumor tissue. Further studies in a mouse model of oral carcinoma are now required to define the mechanisms of the immunotherapeutic effects of the vaccine and to optimize this promising strategy. Using murine antigen presenting cells transfected with DNA from squamous carcinomas, the minimum amount of tumor tissue required to prepare an effective vaccine and the cell types mediating tumor rejection will be determined. The transfected cell-population will be enriched for cells that express TAAs, to increase the therapeutic potential of the vaccine. Its possible toxic effects will be evaluated. These studies will provide insights into the mechanism of tumor rejection and guidelines for optimization of the vaccination strategy. It is expected that development of an effective vaccine to be used alone or in combination with conventional therapy will expand the future therapeutic options available for patients with oral cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013970-02
Application #
6773914
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Bhargava, Sangeeta
Project Start
2003-07-15
Project End
2007-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$272,773
Indirect Cost
Name
University of Illinois at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Lee, Byeong C; Jung, Mi Y; Cho, Daeho et al. (2010) Immunity to Trop-1, a newly identified breast cancer antigen, inhibits the growth of breast cancer in mice. Vaccine 28:7757-63
Cohen, Edward P; Chopra, Amla; O-Sullivan, InSug et al. (2009) Enhancing cellular cancer vaccines. Immunotherapy 1:495-504
Lichtor, Terry; Glick, Roberta P; Feldman, Lisa A et al. (2008) Enhanced immunity to intracerebral breast cancer in mice immunized with a cDNA-based vaccine enriched for immunotherapeutic cells. J Immunother 31:18-27
O-Sullivan, I; Chopra, A; Kim, T S et al. (2007) New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice. Cancer Gene Ther 14:389-98
Spagnolo, Alessandra; Glick, Roberta P; Lin, Henry et al. (2007) Prolonged survival of mice with established intracerebral glioma receiving combined treatment with peroxisome proliferator-activated receptor-gamma thiazolidinedione agonists and interleukin-2-secreting syngeneic/allogeneic fibroblasts. J Neurosurg 106:299-305
Lichtor, Terry; Glick, Roberta P; Lin, Henry et al. (2006) Advantages of a unique DNA-based vaccine in comparison to paclitaxel in treatment of an established intracerebral breast cancer in mice. Cancer Ther 4A:163-170
Lichtor, Terry; Glick, Roberta P; O-Sullivan, Insug et al. (2006) Antigenic Differences Between Normal and Malignant Cells as a Basis for Treatment of Intracerebral Neoplasms Using a DNA-Based Vaccine. Curr Genomics 7:253-261
O-Sullivan, Insug; Kim, Tae Sung; Chopra, Amla et al. (2006) Therapeutic properties of DNA-based fibroblast and dendritic cell vaccines in mice with squamous carcinoma. Anticancer Res 26:873-84
Kim, Tae Sung; Chopra, Amla; O-Sullivan, In Sug et al. (2006) Enhanced immunity to breast cancer in mice immunized with fibroblasts transfected with a complementary DNA expression library from breast cancer cells: Enrichment of the vaccine for immunotherapeutic cells. J Immunother 29:261-73
Chopra, Amla; Kim, Tae Sung; O-Sullivan, Insug et al. (2006) Combined therapy of an established, highly aggressive breast cancer in mice with paclitaxel and a unique DNA-based cell vaccine. Int J Cancer 118:2888-98

Showing the most recent 10 out of 13 publications