This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chakravarty, P. K. Articles by Guha, C. Search for Related Content PubMed PubMed Citation Articles by Chakravarty, P. K. Articles by Guha, C.

Flt3-Ligand Administration after Radiation Therapy Prolongs Survival in a Murine Model of Metastatic Lung Cancer

Departments of Radiation Oncology [P. K. C., A. A., V. B., B. V., C. G.] and Pathology [E. K. T., K. E. T.], Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10461; Beth Israel Medical Center, New York, New York 10003 [A. A.]; and Immunex Corporation, Seattle, Washington 98101 [E. K. T., K. E. T.]

An ineffective tumor-specific immune response from inadequate/incompetent antigen presentation could contribute to the failure in tumor control and its dissemination. Dendritic cells (DCs) have been shown to present antigen from apoptotic cells. We hypothesized that Flt3-ligand (Flt3L) therapy, which expands DCs in vivo, in combination with local tumor radiotherapy (RT), should improve antigen presentation from dying, irradiated tumor cells. RT + Flt3L reduced pulmonary metastases in a murine model of Lewis lung carcinoma and significantly improved survival in C57Bl/6 mice with established footpad tumors. Mice treated with Flt3L alone showed delayed tumor growth but eventually succumbed to tumor progression. The combination therapy of RT + Flt3L failed to impact survival in immunodeficient athymic mice, implicating the role of T cells in prolonging survival. These results support an attractive strategy of sequential RT and immunotherapy with Flt3L to enhance tumor antigen presentation, which may produce therapeutic responses against disseminated cancer and improvement in survival.

This article has been cited by other articles:

				P. J. Dunne, B. Moran, R. C. Cummins, and K. H. G. Mills CD11c+CD8{alpha}+ Dendritic Cells Promote Protective Immunity to Respiratory Infection with Bordetella pertussis J. Immunol., July 1, 2009; 183(1): 400 - 410. [Abstract] [Full Text] [PDF]

				Y. H. Jeon, Y. Choi, S. O. Yoon, C. W. Kim, and J.-K. Chung Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy Mol. Cancer Ther., July 1, 2008; 7(7): 2252 - 2260. [Abstract] [Full Text] [PDF]

				C. Winter, K. Taut, F. Langer, M. Mack, D. E. Briles, J. C. Paton, R. Maus, M. Srivastava, T. Welte, and U. A. Maus FMS-Like Tyrosine Kinase 3 Ligand Aggravates the Lung Inflammatory Response to Streptococcus pneumoniae Infection in Mice: Role of Dendritic Cells J. Immunol., September 1, 2007; 179(5): 3099 - 3108. [Abstract] [Full Text] [PDF]

				A. Mukhopadhaya, J. Mendecki, X. Dong, L. Liu, S. Kalnicki, M. Garg, A. Alfieri, and C. Guha Localized Hyperthermia Combined with Intratumoral Dendritic Cells Induces Systemic Antitumor Immunity Cancer Res., August 15, 2007; 67(16): 7798 - 7806. [Abstract] [Full Text] [PDF]

				U. I. Chaudhry, S. C. Katz, T. P. Kingham, V. G. Pillarisetty, J. R. Raab, A. B. Shah, and R. P. DeMatteo In vivo overexpression of Flt3 ligand expands and activates murine spleen natural killer dendritic cells FASEB J, May 1, 2006; 20(7): 982 - 984. [Abstract] [Full Text] [PDF]

				B. W. Parcells, A. K. Ikeda, T. Simms-Waldrip, T. B. Moore, and K. M. Sakamoto FMS-Like Tyrosine Kinase 3 in Normal Hematopoiesis and Acute Myeloid Leukemia Stem Cells, May 1, 2006; 24(5): 1174 - 1184. [Abstract] [Full Text] [PDF]

				S. Demaria, N. Kawashima, A. M. Yang, M. L. Devitt, J. S. Babb, J. P. Allison, and S. C. Formenti Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer Clin. Cancer Res., January 15, 2005; 11(2): 728 - 734. [Abstract] [Full Text] [PDF]

				B. K. Ambati, A. M. Joussen, J. Ambati, Y. Moromizato, C. Guha, K. Javaherian, S. Gillies, M. S. O'Reilly, and A. P. Adamis Angiostatin Inhibits and Regresses Corneal Neovascularization Arch Ophthalmol, August 1, 2002; 120(8): 1063 - 1068. [Abstract] [Full Text] [PDF]

				S. Demaria, M. D. Volm, R. L. Shapiro, H. T. Yee, R. Oratz, S. C. Formenti, F. Muggia, and W. F. Symmans Development of Tumor-infiltrating Lymphocytes in Breast Cancer after Neoadjuvant Paclitaxel Chemotherapy Clin. Cancer Res., October 1, 2001; 7(10): 3025 - 3030. [Abstract] [Full Text] [PDF]

				C.-F. Hung, K.-F. Hsu, W.-F. Cheng, C.-Y. Chai, L. He, M. Ling, and T-C. Wu Enhancement of DNA Vaccine Potency by Linkage of Antigen Gene to a Gene Encoding the Extracellular Domain of Fms-like Tyrosine Kinase 3-Ligand Cancer Res., February 1, 2001; 61(3): 1080 - 1088. [Abstract] [Full Text]

				R. P. Ciavarra, K. D. Somers, R. R. Brown, W. F. Glass, P. J. d. Consolvo, G. L. Wright, and P. F. Schellhammer Flt3-Ligand Induces Transient Tumor Regression in an Ectopic Treatment Model of Major Histocompatibility Complex-negative Prostate Cancer Cancer Res., April 1, 2000; 60(8): 2081 - 2084. [Abstract] [Full Text]