NDLI: AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above other IL-12 applications

Content Provider	PubMed Central
Author	You, Chang-xuan Shi, Min Liu, Yong Cao, Maohua Luo, Rongcheng Hermonat, Paul L.
Copyright Year	2012
Abstract	Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTL) holds significant promise in treating cancer and Th1 response cytokines are critical for their stimulation. Recently we reported that interleukin 7-(IL-7) and interferongamma-(IFNγ) autocrine/T cell gene delivery resulted in superior ex vivo CTL stimulation over paracrine/DC delivery. IL-12 is yet another important Th1 cytokine which affects both DC and T cells. Here, using adeno-associated virus Type 2 (AAV2) gene delivery, IL-12-paracrine/DC gene delivery gave significantly superior stimulation of carcinoembryonic antigen (CEA)-specific CTL killing over that induced by autocrine gene delivery (or exogenous IL-12 addition). This is surprising as both AAV2/IL-12-treated T cells and DC secreted approximately the same level of IL-12. Paracrine IL-12 gene delivery also resulted in highest IL-12/IL-10 secretion ratio by DC and highest CD40, CD80, CD83 and CD86 expression. Moreover, AAV2/IL-12-DC stimulated the highest T-cell IFNγ production, highest T cell proliferation, highest CD69+/CD8+ levels, and lowest level of CD25+/CD4+ Treg. These data strongly suggest that the primary activity of IL-12 during CTL generation is upon the DC. These data are also consistent with there being novel activity for IL-12 within the DC itself, not involving its surface receptor; an “intracrine” activity. Given the plethora of IL-12 studies, these data also suggest that this gene delivery comparison approach could be useful for uncovering new cytokine activities and mechanism(s) of action gone unrecognized by conventional immunologic assays. Finally, these data further suggest AAV2/IL-12 intracrine gene delivery into DC may have utility in immunotherapy protocols involving antigen-specific CTL.
Related Links	http://dx.doi.org/10.4161/onci.20504
Ending Page	855
Page Count	9
Starting Page	847
File Format	PDF
ISSN	2162402X
e-ISSN	2162402X
Journal	Oncoimmunology
Issue Number	6
Volume Number	1
Language	English
Publisher	Landes Bioscience
Publisher Date	2012-09-01
Access Restriction	Open
Rights Holder	Landes Bioscience
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
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
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

IL-12 Enhances CTL Synapse Formation and Induces Self-reactivity*

IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro.

Human tolerogenic dendritic cells produce IL-35 in the absence of other IL-12 family members

Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12 producers by IL-1β + interferon (IFN)-γ

IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence in a murine model of plasmacytoma

IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL)

A Defect in Nucleosome Remodeling Prevents IL-12(p35) Gene Transcription in Neonatal Dendritic Cells

Induction of IL-10 producing CD4+ T cells with regulatory activities by stimulation with IL-10 gene-modified bone marrow derived dendritic cells

Ibrutinib enhances IL-17 response by modulating the function of bone marrow derived dendritic cells

AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above other IL-12 applications

Similar Documents

IL-12 Enhances CTL Synapse Formation and Induces Self-reactivity*

IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro.

Human tolerogenic dendritic cells produce IL-35 in the absence of other IL-12 family members

Engagement of human monocyte-derived dendritic cells into interleukin (IL)-12 producers by IL-1β + interferon (IFN)-γ

IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4+ T cells and promoting CTL persistence in a murine model of plasmacytoma

IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL)

A Defect in Nucleosome Remodeling Prevents IL-12(p35) Gene Transcription in Neonatal Dendritic Cells

Induction of IL-10 producing CD4+ T cells with regulatory activities by stimulation with IL-10 gene-modified bone marrow derived dendritic cells

Ibrutinib enhances IL-17 response by modulating the function of bone marrow derived dendritic cells

AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above other IL-12 applications