Grants and Contracts Details
Description
Lung cancer is the leading killer due to cancer of men and women in the United States. Conventional therapies
are limited in their ability to impact the disease. Patients treated with the chemotherapeutic drug Cisplatin, often
re-occur even following what appear to be significant durable responses. Cisplatin binds to DNA and forms
adducts, thus preventing DNA synthesis, transcription and eventual translation of critical cellular proteins
associated with the neoplastic state. Resistant tumor cells, however, evolve mechanisms to: 1) prevent drug
uptake into the cytoplasm, 2) increase drug efflux fTomthe cytoplasm out of the cell, 3) immobilize drug in the
cytoplasm, and 4) repair damage done by DNA adducts formed as a result of drug binding to the DNA. The
current proposal suggests that the proteins that the tumor cells express to maintain the chemo-resistant phenotype
can serve as targets for the immune system, specifically cytotoxic T lymphocytes (CTL). The PI has developed a
unique model system ofNSCLC tumor cell lines and associated clones which express both Cisplatin sensitive
and resistant phenotype. The proposal will utilize the Cisplatin resistant tumor cell clones to generate CTL which
can recognize and kill resistant tumor cells. The PI suggests a future immunotherapy strategy where-by patients
are immunized using DC vaccines which express proteins associated with the chemo-resistant state. Following
chemotherapy with the specific agent, the patients will be boosted with DC vaccines, thus increasing the CTL
precursor frequency against those tumor cells which will eventually develop Cisplatin resistance. The current
study is for 2 years and will provide the PI with critical "Proof of Principal" data that the hypothesis is well
founded and feasible. The data generated will be used to submit an RO-l and eventually utilized to develop new
and innovative immunotherapies for patients with this deadly disease.
Status | Finished |
---|---|
Effective start/end date | 9/1/07 → 8/31/09 |
Funding
- KY Lung Cancer Research Fund: $144,086.00
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