The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Le, H. N.
Right arrow Articles by Norton, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Le, H. N.
Right arrow Articles by Norton, J. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CYCLOPHOSPHAMIDE
The Journal of Immunology, 2001, 167: 6765-6772.
Copyright © 2001 by The American Association of Immunologists

Pre-Existing Tumor-Sensitized T Cells Are Essential for Eradication of Established Tumors by IL-12 and Cyclophosphamide Plus IL-121

Hop N. Le, Natalie C. Lee, Kangla Tsung2 and Jeffrey A. Norton

Department of Surgery, University of California and San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121

The antitumor immune response activated by IL-12, especially by a combination of cyclophosphamide and IL-12 (Cy+IL-12), is clinically significant in certain experimental tumor models, in that a number of well-established (10–20 mm in diameter) s.c. tumors are completely eradicated. Furthermore, Cy+IL-12 treatment is also able to eradicate well-established grossly detectable experimental lung metastases and advanced ascites tumors. Despite the dramatic antitumor effects seen in some tumor models, Cy+IL-12 fails to induce regression of other established tumors. Characterization of tumor immunogenicity shows that all tumors responding to IL-12 and Cy+IL-12 treatments are immunogenic tumors, in that an antitumor immune response is detectable in tumor-bearing hosts upon tumor establishment. In contrast, none of the nonimmunogenic tumor responds to IL-12 and Cy+IL-12 treatments. Analysis of cellular requirements for successful tumor rejection through an adoptive cell transfer approach reveals that the presence of tumor-sensitized, but not naive, T cells is essential for tumor rejection by IL-12 and Cy+IL-12. Transfer of these tumor-sensitized T cells must be conducted before, but not after, IL-12 treatment in order for tumor rejection to occur. The requirement of sensitized T cells is also tumor specific. In mice bearing immunogenic tumors, the presence of pre-existing tumor-sensitized T cells is demonstrated by adoptive cell transfer experiments using purified spleen T cells from these mice. Results from our study show that Cy+IL-12-based immunotherapy of cancer may be highly effective and that pre-existing tumor-sensitized T cells are essential for the success of the therapy.




This article has been cited by other articles:


Home page
 J. Virol.Home page
M. Robinson, B. Li, Y. Ge, D. Ko, S. Yendluri, T. Harding, M. VanRoey, K. R. Spindler, and K. Jooss
Novel Immunocompetent Murine Tumor Model for Evaluation of Conditionally Replication-Competent (Oncolytic) Murine Adenoviral Vectors
J. Virol., April 15, 2009; 83(8): 3450 - 3462.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. N. Rad, G. Pollara, S. M. A. Sohaib, C. Chiang, B. M. Chain, and D. R. Katz
The Differential Influence of Allogeneic Tumor Cell Death via DNA Damage on Dendritic Cell Maturation and Antigen Presentation
Cancer Res., August 15, 2003; 63(16): 5143 - 5150.
[Abstract] [Full Text] [PDF]

Home page
 Arch Otolaryngol Head Neck SurgHome page
A. H. Mandpe, K. Tsung, and J. A. Norton
Cure of an Established Nonimmunogenic Tumor, SCC VII, With a Novel Interleukin 12-Based Immunotherapy Regimen in C3H Mice
Arch Otolaryngol Head Neck Surg, July 1, 2003; 129(7): 786 - 792.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. D. Hess, N. K. Egilmez, N. Bailey, T. M. Anderson, E. Mathiowitz, S. H. Bernstein, and R. B. Bankert
Human CD4+ T Cells Present Within the Microenvironment of Human Lung Tumors Are Mobilized by the Local and Sustained Release of IL-12 to Kill Tumors In Situ by Indirect Effects of IFN-{gamma}
J. Immunol., January 1, 2003; 170(1): 400 - 412.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. C. Hill, T. F. Conway Jr., M. S. Sabel, Y. S. Jong, E. Mathiowitz, R. B. Bankert, and N. K. Egilmez
Cancer Immunotherapy with Interleukin 12 and Granulocyte-Macrophage Colony-stimulating Factor-encapsulated Microspheres: Coinduction of Innate and Adaptive Antitumor Immunity and Cure of Disseminated Disease
Cancer Res., December 15, 2002; 62(24): 7254 - 7263.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Tsung, J. P. Dolan, Y. L. Tsung, and J. A. Norton
Macrophages as Effector Cells in Interleukin 12-induced T Cell-dependent Tumor Rejection
Cancer Res., September 1, 2002; 62(17): 5069 - 5075.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. G. Segal, N. C. Lee, Y. L. Tsung, J. A. Norton, and K. Tsung
The Role of IFN-{gamma} in Rejection of Established Tumors by IL-12 : Source of Production and Target
Cancer Res., August 15, 2002; 62(16): 4696 - 4703.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.