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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 747 - 763 (17page)
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Purpose Successful tumor eradication primarily depends on generation and maintenance of a large population of tumor-reactive CD8 T cells. Dendritic cells (DCs) are well-known potent antigen- presenting cells and have applied to clinics as potent antitumor therapeutic agents. However, high cost and difficulty in obtaining sufficient amounts for clinical use are the crucial drawbacks of DC-based vaccines. Here, we aimed to develop T cell–based vaccine capable of eliciting potent antitumor therapeutic effects by providing effective costimulatory signals. Materials and Methods Antigenic peptide-loaded T cells transfected with retrovirus encoding costimulatory ligands CD70, CD80, OX40L, or 4-1BBL were assessed for antigen-specific CD8 T-cell responses and evaluated antitumor effects along with immunization of a mixture of synthetic peptides, poly-IC and anti-CD40 antibodies (TriVax). Results T cells expressing CD70 (CD70-T) exhibited similar level of stimulatory functionality and therapeutic efficacy as DCs. Moreover, CD70-T prime followed by TriVax booster heterologous vaccination elicited therapeutic antitumor effect against B16 melanoma where mediated by CD8 T cells but not CD4 T cells or natural killer cells. The combination with programmed death-ligand 1 blockade led to potent therapeutic efficacy which exhibited increased tumor-infiltrating CD8 T cells. CD70-T pulsed with multi-antigenic peptide generated multiple antigen-specific polyvalent CD8 T cells that were capable of inhibiting tumor growth effectively. Moreover, CD70-T vaccination resulted in higher expansion and migration of adoptively transferred T cells into tumor sites and elicits enhanced therapeutic effects with peptide-based booster immu-nization. Conclusion These results imply that T cells endowed with CD70 enable the design of effective vaccination strategies against solid cancer, which may overcome current limitations of DC-based vaccines.
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참고문헌 (38)
참고문헌 신청
Croft M / 2003 / Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? / Nat Rev Immunol 3:609~620
Thery C / 2001 / The cell biology of antigen presentation in dendritic cells / Curr Opin Immunol 13:45~51
Cho HI / 2015 / An optimized peptide vaccine strategy capable of inducing multivalent CD8(+)T cell responses with potent antitumor effects / Oncoimmunology 4:e1043504
Liu Y / 2002 / Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8(+)cytotoxic T-cell activation and antitumor immunity / Cancer Gene Ther 9:202~208
Mende I / 2005 / Breaking tolerance to tumors with dendritic cell-based immunotherapy / Ann N Y Acad Sci 1058:96~104
Thery C / 2001 / The cell biology of antigen presentation in dendritic cells / Curr Opin Immunol 13:45~51
Cho HI / 2015 / An optimized peptide vaccine strategy capable of inducing multivalent CD8(+)T cell responses with potent antitumor effects / Oncoimmunology 4:e1043504
Liu Y / 2002 / Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8(+)cytotoxic T-cell activation and antitumor immunity / Cancer Gene Ther 9:202~208
Mende I / 2005 / Breaking tolerance to tumors with dendritic cell-based immunotherapy / Ann N Y Acad Sci 1058:96~104
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