Given the plateau in progress made with conventional treatment modalities for many cancers, novel treatment modalities need to be developed. Immunotherapy is an example. Over the past 8 years the Candidate has built an effective infrastructure for conducting investigator-initiated, gene-modified, cell- based vaccines for the treatment of a variety of cancers. This program was recently identified by the Moffitt senior leadership as one of 5 high priority programs that the cancer center will be supporting, and the Candidate was recently named Co-Program Leader of the Immunology and Immunotherapy Program. With this fully functional infrastructure, experienced staff along with the basic and clinical research scientists can begin with a scientific hypothesis, create the appropriate therapeutics needed to test the hypothesis, perform proof-of-principle experiments in the preclinical setting, perform the safety and characterization testing in support of 1ND applications, scale up and manufacture the immunotherapeutics, negotiate all of the required regulatory agency review, conduct the clinical trial, monitor the clinical and immunologic effects of the strategy, and generate new hypotheses based on the results of the clinical trials that are tested in the basic research laboratories. Two main vaccines have produced evidence of efficacy in early phase trials. The research proposed will move these vaccines forward, combining them with tumor vaccine augmentation strategies in lung cancer patients. The vaccines are (1) a dendritic cell-based vaccine using p53 as the tumor antigen, and (2) a GM-CSF and CD40 ligand-expressing bystander cell line admixed with tumor cells as the source of tumor antigens. The augmentation strategies targeting the immunosuppressive effects of tumor cells are: (1) ATRA, (2) 1-methyl tryptophan (IDO inhibitor), and (3) lymphodepletion to eliminate T reg cells and induce homeostatic T cell proliferation. The candidate is currently mentoring 7 Oncology Fellows and Assistant Professors in developing and conducting 10 clinical trials involving these approaches. The Moffitt Cancer Center has a large clinical volume (200,000 clinic visits per year) which allows for rapid accrual to trials. There continues to be steady growth, and so there is a plan to recruit 5 faculty this year and then 3 per year over the next 5 years. This will provide an excellent source of potential mentees, along with the Hematology and Oncology, and Surgical Oncology Fellowship training programs. An institutional K12 grant is in place to support protected time for these individuals to perform research, and the institution was recently awarded a K30 to support patient oriented clinical research training. The current grant would allow the Candidate to be excused from numerous administrative responsibilities and allow him to commit more effort to conducting clinical research and mentoring, which is necessary given the dramatic expansion of the Immunotherapy Program over the past several years.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24CA128953-05
Application #
8311051
Study Section
Subcommittee G - Education (NCI)
Program Officer
Lim, Susan E
Project Start
2008-09-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$171,205
Indirect Cost
$12,682
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
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Finkelstein, Steven Eric; Rodriguez, Francisco; Dunn, Mary et al. (2012) Serial assessment of lymphocytes and apoptosis in the prostate during coordinated intraprostatic dendritic cell injection and radiotherapy. Immunotherapy 4:373-82
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Bui, Marilyn M; Zheng, Zhong; Antonia, Scott et al. (2010) Thymidylate synthase 1 (TS1) in-situ protein expression predicts the survival of Ewing/PNET. Fetal Pediatr Pathol 29:385-92
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Chiappori, Alberto A; Soliman, Hatem; Janssen, William E et al. (2010) INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther 10:983-91

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