ASGSB 1998 Annual Meeting Abstracts

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POTENTIAL USE OF NASA BIOREACTORS IN PRODUCTION OF CANCER VACCINES.   D. Yetman¹, S. P. Tomasovic¹, and C.A. Savary². Depts. of ¹Tumor Biology and ²Surgical Oncology, Univ. of Texas M.D. Anderson Cancer Center, Houston.

Previous studies have shown that tumor-associated antigens are better expressed when malignant cells are grown in 3-dimensional (3D) environments, as opposed to standard monolayer conditions. This suggested to us that human carcinomas grown in 3D NASA bioreactors might be a better source of antigen for preparation of tumor vaccines. Recent attention has been drawn to the use of heat shock proteins (Hsp) for vaccination against cancer. In their role as molecular chaperones, Hsp bind to many proteins, including tumor-associated peptides. This could explain why Hsp-peptide complexes extracted from murine tumors were found to have both therapeutic and protective potential in mice challenged with the same tumor. Neither Hsp nor peptide alone was effective, suggesting that Hsp are acting as a natural adjuvant. Early clinical trials of Hsp-peptides in treatment of cancer patients have shown promising effects. However, the amount of complexes available for vaccination and subsequent boosting is expected to be limited to the size and viability of each patient’s tumor at surgery. In certain cancers, e.g. breast cancer, the tumor volume may be quite low, so that alternate approaches will be needed to generate enough Hsp-peptide for vaccination. We have found that the NASA bioreactors support the anchorage-independent growth of the HER-2/neu gene-transfected eB.1 breast carcinoma line. Moreover, these cells were found to express a higher level of Hsp70 compared to 2D monolayer controls as evaluated by Western blotting and flow cytometry.

Using the HER-2/neu-encoded p185 protein as a surrogate tumor-associated marker, we are currently evaluating whether Hsp70-p185 complexes are increased in parallel in the 3D cultured eB.1 cells. If this is found to be the case, our data could suggest that tumors expanded in NASA bioreactors might allow for continuous, upscaled production of Hsp-peptides for therapeutic and/or vaccination purposes, and might allow for treatment of patients who would not otherwise qualify for this promising new therapy. (Supported by NASA: NAG8-1347.)

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