RRC ID 12190
Author Nishisaka N, Maini A, Kinoshita Y, Yasumoto R, Kishimoto T, Jones RF, Morse P, Hillman GG, Wang CY, Haas GP.
Title Immunotherapy for lung metastases of murine renal cell carcinoma: synergy between radiation and cytokine-producing tumor vaccines.
Journal J Immunother
Abstract We investigated the combination therapy of local radiation of lung metastasis and vaccination with autologous tumor cells that produced interleukin (IL)-2, interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) using the mouse Renca pulmonary metastasis model. Wild-type Renca (W/Renca) were transfected with pEF-BOS vector incorporating cDNAs for IL-2, IFN-gamma, or GM-CSF to express these cytokines. W/Renca, IL-2-producing Renca (Renca/IL-2), and IFN-gamma-producing Renca (Renca/IFN-gamma) produced subcutaneous tumor at the injection site in eight of eight, one of eight, and two of eight mice, respectively. No tumors were found in the GM-CSF-producing Renca (Renca/GM-CSF) group (zero of eight). Renca/IFN-gamma produced subcutaneous (s.c.) tumors in all Balb/c nude mice, but Renca/IL-2 and Renca/GM-CSF did not. To test the elicitation of antitumor activity, Balb/c mice were injected intravenously with 1 x 10(5) W/Renca on day 0, vaccinated, s.c., with 1 x 10(6) cells each of 5,000 rad preirradiated Renca/IL-2, Renca/IFN-gamma, and Renca/GM-CSF or 3 x 10(6) cells of preirradiated W/Renca on days 1, 7, and 14, and radiated with 300 rad to both lungs on day 5. The animals were killed on day 21 and tumor nodules in the lungs were enumerated. Neither local irradiation alone nor the combination of lung radiation and multiple vaccination with irradiated W/Renca significantly reduced the number of lung tumors. In contrast, the combination of lung radiation and the multiple vaccinations with cytokine-producing Renca cells significantly reduced the number of lung tumors. This regimen was more effective than the multiple vaccinations with cytokine-producing Renca cells alone. These studies demonstrate the efficacy of vaccination with autologous tumor cells expressing these cytokines and sensitization of the tumor target with radiation.
Volume 22(4)
Pages 308-14
Published 1999-7-1
DOI 10.1097/00002371-199907000-00004
PMID 10404432
MeSH Animals Cancer Vaccines / pharmacology Cancer Vaccines / therapeutic use* Carcinoma, Renal Cell / radiotherapy Carcinoma, Renal Cell / secondary* Carcinoma, Renal Cell / therapy* Combined Modality Therapy Cytokines / immunology* Cytokines / metabolism Drug Synergism Female Granulocyte-Macrophage Colony-Stimulating Factor / immunology Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Immunity, Cellular / drug effects Immunity, Cellular / immunology Interferon-gamma / immunology Interferon-gamma / metabolism Interleukin-2 / immunology Interleukin-2 / metabolism Kidney Neoplasms / pathology Kidney Neoplasms / radiotherapy Kidney Neoplasms / therapy Lung Neoplasms / radiotherapy Lung Neoplasms / secondary* Lung Neoplasms / therapy* Mice Mice, Inbred BALB C
IF 4.11
Times Cited 18
DNA material pMFGmIL2 (RDB01441) pMFGmIFN gamma (RDB01454) pBluescript SKII+mGM-CSF Mouse GM-CSF cDNA (RDB01469)