CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity |
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Authors: | Hidekazu Shirota Dennis M Klinman |
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Institution: | (1) Basic Science Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD, USA;(2) Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, Bldg 567 Rm 205, NCI in Frederick, Frederick, MD 21702, USA |
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Abstract: | The primary goal of cancer immunotherapy is to elicit an immune response capable of eradicating established tumors and preventing
tumor metastasis. One strategy to achieve this goal utilizes whole killed tumor cells as the primary immunogen. Killed tumor
cells provide a comprehensive source of tumor-associated antigens (TAAs), thereby eliminating the need to identify individual
antigens. Unfortunately, killed tumor cells tend to be poorly immunogenic. To overcome this limitation, we covalently conjugated
immunostimulatory CpG oligodeoxynucleotides (ODN) to apoptotic tumor cells and examined their ability to induce TAA-specific
immune responses. Results indicate that CpG conjugation enhances the uptake of cell-based vaccines by dendritic cells (DCs),
up-regulates co-stimulatory molecule expression, and promotes the production of immunostimulatory cytokines. Vaccination with
CpG-conjugated tumor cells triggers the expansion of tumor-specific cytotoxic T lymphocytes (CTL) that reduce the growth of
established tumors and prevents their metastatic spread. Thus, conjugating CpG ODN to cell-based tumor vaccines is an important
step toward improving cancer immunotherapy. |
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