摘要
Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8<sup>+</sup>CD28<sup>+</sup> cytotoxic T lymphocyte(CTL) responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated with H-2K<sup>b</sup>:Ig-TRP2<sub>(</sub>1811<sub>1</sub>1K<sub> </sub>and anti-CD28 antibody were used as artificial antigen-presenting cells(aAPCs) lo induce melanoma-specific CD8*CD28’ CTL responses with the help of IL-2I and IL-I5.Dimer staining,proliferation,ELISPOT,and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.Results:Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8CD28' CTLs.Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- y under the slimulalion of H-2K:Ig-TRP2-aAPCs,TL-15,and IL-21.In addition,cytoloxicily experiments showed lhat induced CTLs have specific killing activity of target cells.Conclusions:The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8<sup>+</sup>CD28<sup>+</sup> CTLs against the melanoma.Our study provides evidence for a novel adoptive immunotherapy against tumors.
Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8+CD28+ cytotoxic T lymphocyte(CTL) responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated with H-2Kb:Ig-TRP2(181111K and anti-CD28 antibody were used as artificial antigen-presenting cells(aAPCs) lo induce melanoma-specific CD8*CD28’ CTL responses with the help of IL-2I and IL-I5.Dimer staining,proliferation,ELISPOT,and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.Results:Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8CD28' CTLs.Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- y under the slimulalion of H-2K:Ig-TRP2-aAPCs,TL-15,and IL-21.In addition,cytoloxicily experiments showed lhat induced CTLs have specific killing activity of target cells.Conclusions:The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8+CD28+ CTLs against the melanoma.Our study provides evidence for a novel adoptive immunotherapy against tumors.
基金
supported,in part,by grants from the Program for New Century Excellent Talents in University(NECT-10-0098)
the National Natural Scientific Foundation of China(Nos.81072161.81000769.81172139.and 81060183)
Programs for Changjiang Scholars and Innovative Research Team in University(No. IRT1119)
Innovative Research Team in Guangxi Natural Science Foundation (No.2011-18-5)
Fund for Distinguished Young Scholars in Guangxi Natural Science Foundation(2012jjFA40005)
Project of science and technology of Guangxi (1140003A-17)