Artificial antigen-presenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8⁺ CD28⁺ T lymphocyte responses

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• 作者：Xia Yu^a ; ^¦¤ ; Jian He^a ; ^¦¤ ; Sodaly Mongkhoune^a ; ^¦¤ ; Yi Peng^a ; Yuan Xie^a ; Jing Su^a ; Su-Fang Zhou^a ; Xiao-Xun Xie^a ; Guo-Rong Luo^a ; Yuan Fang^a ; Xi Li^a ; Xi Li^a ; Nuo Zhou^a ; ^b ; ^{nuozhou@hotmail.com} ; Yong-Xiang Zhao^a ; ^c ; ^{yongxiang_zhao@126.com} ; Xiao-Ling Lu^a ; ^c ; ^c ; ^{luwuliu@163.com}
• 关键词：IL-21 ; IL-15 ; Artificial antigen-presenting ; TRP2-specific CD8
• 刊名：Asian Pacific Journal of Tropical Medicine
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：6
• 期：6
• 页码：467-472
• 全文大小：672 K

文摘

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-2K^b: Ig-TRP2_180-188and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8⁺CD28⁺ CTL responses with the help of IL-21 and IL-15. 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 CD8⁺CD28⁺CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- ¦Ã under the stimulation of H-2K^b: Ig-TRP2-aAPCs, IL-15, and IL-21. In addition, cytotoxicity experiments showed that 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.