NDLI: IL-21 augments the efficacy of T cell therapy by eliciting concurrent cellular and humoral responses1

Content Provider	PubMed Central
Author	Iuchi, Takekazu Seagal, Teitz-tennenbaum Huang, Jianhua Redman, Bruce G. Hughes, Steven D. Li, Mu Jiang, Guihua Chang, Alfred E. Li, Qiao
Abstract	Interleukin (IL)-21 modulates T cell, B cell, and NK cell-associated immunity. However, the potential of IL-21 to simultaneously stimulate cellular and humoral antitumor responses and the mechanisms involved have not yet been adequately explored. In this report, we examined the immune modulating effect of IL-21 when used in vitro and its adjuvant effects when administrated concomitantly with T cell transfer for cancer therapy. Use of IL-21 in concert with IL-2 in culture up-regulated both type 1 and type 2 cytokine production of activated tumor-draining lymph node (TDLN) cells and enhanced their therapeutic efficacy. Administration of IL-21 and IL-2 as an adjuvant to T cell transfer resulted in simultaneously elicited cellular and humoral responses. This concurrent response has led to effective regression of established pulmonary metastatic tumors and subcutaneous tumors. T cell transfer plus IL-21/IL-2 administration conferred systemic immunity to the treated hosts. This was evident by the induction of protective immunity against tumor re-challenge; expansion of memory T cells, and significantly elevated serum levels of IFNγ and IL-10. Furthermore, we observed significantly enhanced tumor-associated antibody response after T cell+IL-2+IL-21 therapy. Cytotoxic antibody subclass IgG2b increased strikingly in the sera of treated animals; they bound specifically to MCA205 tumor cells, and such immune sera mediated tumor cell lysis in the presence of complement. Use of B cell-deficient mice provided direct evidence that humoral responses contribute to T cell+IL-2+IL-21-elicited antitumor immunity. Collectively, these findings provide a rationale to evaluate the use of IL-21 in T cell therapy of human cancers.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-07-5530
Ending Page	4441
Page Count	11
Starting Page	4431
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	11
Volume Number	68
Language	English
Publisher Date	2008-06-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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