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More Efficient Induction of HLA-A*0201-Restricted and Carcinoembryonic Antigen (CEA)–Specific CTL Response by Immunization with Exosomes Prepared from Heat-Stressed CEA-Positive Tu...
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| Zeitschriftentitel: | Clinical Cancer Research |
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| Personen und Körperschaften: | , , , , , , , |
| In: | Clinical Cancer Research, 11, 2005, 20, S. 7554-7563 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>Purpose: Tumor-derived exosomes are proposed as a new type of cancer vaccine. Heat shock proteins are potent Th1 adjuvant, and heat stress can induce heat shock protein and MHC-I expression in tumor cells, leading to the increased immunogenicity of tumor cells. To improve the immunogenicity of exosomes as cancer vaccine, we prepared exosomes from heat-stressed carcinoembryonic antigen (CEA)–positive tumor cells (CEA+/HS-Exo) and tested the efficacy of these exosomes in the induction of CEA-specific antitumor immunity.</jats:p><jats:p>Experimental Design: First, we identified the composition of CEA+/HS-Exo and observed their effects on human dendritic cell maturation. Then, we evaluated their ability to induce a CEA-specific immune response in vivo in HLA-A2.1/Kb transgenic mice and CEA-specific CTL response in vitro in HLA-A*0201+ healthy donors and HLA-A*0201+CEA+ cancer patients.</jats:p><jats:p>Results: CEA+/HS-Exo contained CEA and more heat shock protein 70 and MHC-I and significantly induced dendritic cell maturation. Immunization of HLA-A2.1/Kb transgenic mice with CEA+/HS-Exo was more efficient in priming a CEA-specific CTL, and the CTL showed antitumor effect when adoptively transferred to SW480-bearing nude mice. Moreover, in vitro incubation of lymphocytes from HLA-A*0201+ healthy donors and HLA-A*0201+CEA+ cancer patients with CEA+/HS-Exo-pulsed autologous dendritic cells induces HLA-A*0201-restricted and CEA-specific CTL response.</jats:p><jats:p>Conclusions: Our results show that CEA+/HS-Exo has superior immunogenicity than CEA+/Exo in inducing CEA-specific CTL response and suggest that exosomes derived from heat-stressed tumor cells may be used as efficient vaccine for cancer immunotherapy.</jats:p> |
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| Umfang: | 7554-7563 |
| ISSN: |
1078-0432
1557-3265 |
| DOI: | 10.1158/1078-0432.ccr-05-0810 |