Epigenetically-Modified Autologous Tumor Cell Vaccines With ISCOMATRIX(TM) Adjuvant and Oral Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thoracic Sarcomas, and Malignant Pleural Mesotheliomas
- Cancer-testis (CT) antigens have emerged as attractive targets for cancer
immunotherapy. Whereas lung and esophageal cancers, primary thoracic sarcomas, as well
as malignant pleural mesotheliomas express a variety of CT antigens, primary or
vaccine-induced immune responses to these antigens appear uncommon in patients with
these malignancies, possibly due to low-level, heterogeneous antigen expression, and
inadequate vaccination strategies.
- Because numerous CT antigens can be induced in tumor cells by DNA demethylating agents
and HDAC inhibitors, it is conceivable that vaccination of cancer patients with
autologous tumor cells exposed to chromatin remodeling agents will enhance anti-tumor
immunity in these individuals.
- In order to examine this issue, patients with resectable primary neoplasms involving
the lungs, esophagus, or pleura will be vaccinated with autologous tumor cells exposed
exvivo to decitabine and radiation following completion of appropriate combined
modality therapy. Vaccine will be administered in conjunction with
ISCOMATRIX(Trademark) adjuvant and oral celecoxib.
- To assess the safety of an epigenetically modified autologous tumor cell vaccine in
conjunction with celecoxib.
- Patients with histologically or cytologically proven primary pulmonary carcinoma or
sarcoma, esophageal cancer, or malignant pleural mesothelioma undergoing resection of
- Patients must be 18 years or older with an ECOG performance status of 0 - 2, with
adequate pulmonary and cardiac function and laboratory values within normal limits.
- Patients with operable lung and esophageal carcinoma/sarcoma, or malignant pleural
mesothelioma will undergo resection of their malignancies at the NCI.
- Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory
and cells will be processed to establish a cancer cell line.
- Following recovery from surgery and appropriate adjuvant chemotherapy and/or radiation,
patients will be vaccinated with epigenetically-modified autologous tumor cells
periodically over 6 months in conjunction with oral celecoxib.
- Systemic toxicities and delayed type hypersensitivity responses to autologous tumor
cells and serologic responses to a variety of CT antigens will be assessed before and
- Patients will be followed with routine staging scans until disease recurrence.
- As the exact set of comparisons and analyses to be performed will be determined
following completion of the trial, and will be based on limited numbers of patients,
the analyses will be considered exploratory and hypothesis generating rather than
- Approximately 120 patients will be accrued to this trial in order to obtain up to 30
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of the tumor cell vaccine administered with ISCOMATRIX(TM) adjuvant and oral celecoxib.
David S Schrump, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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