CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity

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...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2011-05, Vol.60 (5), p.659-669
Main Authors: Shirota, Hidekazu, Klinman, Dennis M.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Animals
Antigens
Antigens, Neoplasm - immunology
Antineoplastic agents
Apoptosis
Biological and medical sciences
Cancer
Cancer Research
Cancer Vaccines - immunology
CpG Islands
Cytokines - genetics
Cytotoxicity, Immunologic
Dendritic Cells - immunology
Dendritic Cells - metabolism
Flow Cytometry
Immune system
Immunology
Immunotherapy
Medical research
Medical sciences
Medicine
Medicine & Public Health
Metastasis
Mice
Mice, Inbred C57BL
Neoplasm Metastasis - immunology
Neoplasm Metastasis - prevention & control
Neoplasm Metastasis - therapy
Neoplasms - immunology
Neoplasms - therapy
Oligodeoxyribonucleotides - immunology
Oncology
Original Article
Pharmacology. Drug treatments
Proteins
T-Lymphocytes, Cytotoxic - immunology
Tumor Cells, Cultured
Tumors
Vaccines
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Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-011-0973-y