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Translational and Clinical Research/ N' W3 C$ F5 Q( Y/ o
Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer§
7 [6 {# D4 \, vYi Li 1 4, Hui Zeng 2 3 5, Ren-He Xu 2 3, Bei Liu 1 2 *¶, Zihai Li 1 2 *||
: D) A# P& X9 _7 |0 A* ^1Department of Immunology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
8 p- e" Y. M1 ~' o2UConn Stem Cell Institute, and University of Connecticut School of Medicine, Farmington, Connecticut, USA) l6 R- k2 M7 z5 G, S; ~
3Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, Connecticut, USA
$ R1 ~; P7 u' ]0 ~8 A4Department of Gynecology and Obstetrics, Peking University People's Hospital, Beijing, People's Republic of China* @( B7 l, j0 z F
5Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China
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d+ T# J/ ^2 M7 [3 Memail: Bei Liu (bliu@up.uchc.edu) Zihai Li (Zihai@uchc.edu) ) e7 d( [) u) T& {% H
4 l0 z2 k, ?3 a6 I*Correspondence to Bei Liu, Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA' B/ n7 g5 `' j( J4 n3 L* M
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*Correspondence to Zihai Li, Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA
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( t; u7 X/ |+ P! ^Author contributions: Y.L.: collection and/or assembly of data, data analysis and interpretation; manuscript writing; H.Z.: generation, maintenance, and characterization of stem cells, manuscript writing; R.-H.X.: data analysis and interpretation, provision of study material, financial support, final approval of manuscript; B.L.: conception and design, collection and/or assembly of data, data analysis and interpretation, financial support, manuscript writing; Z.L.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.. O$ p1 Y9 \3 ~, b6 `
First published online in STEM CELLS EXPRESS October 8, 2009.
( E# p! S# J N* G§Disclosure of potential conflicts of interest is found at the end of this article.
% Z; K5 l% |) d# H# g, Z$ W; R¶Telephone: +1-860-679-7979; Fax: +1-860-679-8130. S3 E, ?& b9 N& c( W' k
||Telephone: +1-860-679-7979; Fax: +1-860-679-81300 F2 f+ r# y- |
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Funded by:
* @# M+ k' V* F% p- m$ G Connecticut Stem Cell Research Grants Program; Grant Number: 06SCA031, 06SCD026 e1 j0 b2 D3 `. v% l) Q
University of Connecticut School of Medicine: `1 Z x. u# h6 P
Leukemia and Lymphoma Society
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; x, R( O. n) l: P; P2 ~Keywords
- a C* L3 O* x4 c. r# M4 e+ h" M7 ~Embryonic stem cells • Induced pluripotent stem cells • Cancer vaccine • Oncofetal antigen • Myeloid-derived suppressor cells
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2 N3 q; n$ N5 R2 @Abstract , J5 u2 j- U8 Q# ^
The history of immunizing with embryonic materials to generate an antitumor immune response dates back to a century ago. The premise is that cancer cells share the expression of oncofetal antigens with embryonic materials and that the immune response against these antigens in the embryonic tissues is cross-protective against cancer. However, such a practice has never advanced beyond experimental animal settings, because of lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask whether tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated whether vaccination with defined human embryonic stem cells (hESCs) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hESC line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon--producing cells and the profound loss of CD11b+Gr-1+ myeloid-derived suppressor cells in the spleen. No evidence of autoimmunity was observed. We also compared the immunogenicity against colon cancer between a hESC line CT2 and an iPS cell line TZ1 that were generated in the same stem cell facility. We found that the iPS cell line was inferior to the hESC line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hESCs and iPS cells. We conclude that the hESC-based vaccine is a promising modality for immunotherapy of cancer.
4 }) E, b) ] M' h/ ^* i4 t3 p& R$ `STEM CELLS 2009;27:3103-3111 |
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发表于 2010-4-7 13:43
