Synergistic effect of interleukin-15 and interleukin-12 on antitumor activity in a murine malignant pleurisy model

2000 ◽  
Vol 49 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Keiko Kimura ◽  
Hitoshi Nishimura ◽  
Takeshi Matsuzaki ◽  
Teruo Yokokura ◽  
Yuji Nimura ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Synergistic Effect ◽  
Interleukin 12 ◽  
Interleukin 15 ◽  
Malignant Pleurisy

scholarly journals Effects of Interleukin-12 and Interleukin-15 on Measles-Specific T-Cell Responses in Vaccinated Infants

2008 ◽  
Vol 21 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Hayley A. Gans ◽  
Linda L. Yasukawa ◽  
Cathryn Z. Zhang ◽  
Rima Hanna Wakim ◽  
Mary Rinki ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Interleukin 12 ◽  
Cell Responses ◽  
Interleukin 15

scholarly journals Transfection of the genes for interleukin-12 into the K1735 melanoma and the EMT6 mammary sarcoma murine cell lines reveals distinct mechanisms of antitumor activity

2003 ◽  
Vol 106 (5) ◽  
pp. 690-698 ◽  
Author(s):  
James P. Moran ◽  
Scott A. Gerber ◽  
Celeste A. Martin ◽  
John G. Frelinger ◽  
Edith M. Lord
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Interleukin 12 ◽  
Murine Cell

Antitumor Activity of Killer Cells Stimulated with Both Interleukin-2 and Interleukin-12 on Mouse Glioma Cells

1999 ◽  
Vol 22 (3) ◽  
pp. 245-250 ◽  
Author(s):  
Tetsuro Kikuchi ◽  
Tatsuhiro Joki ◽  
Toshiaki Abe ◽  
Tsuneya Ohno
Keyword(s):  
Antitumor Activity ◽  
Interleukin 2 ◽  
Glioma Cells ◽  
Interleukin 12 ◽  
Killer Cells ◽  
Mouse Glioma

scholarly journals Co-delivery of doxorubicin, docosahexaenoic acid, and α-tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity

2020 ◽  
Vol 132 ◽  
pp. 110876
Author(s):  
Eduardo Burgarelli Lages ◽  
Renata Salgado Fernandes ◽  
Juliana de Oliveira Silva ◽  
Ângelo Malachias de Souza ◽  
Geovanni Dantas Cassali ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Docosahexaenoic Acid ◽  
Synergistic Effect ◽  
Nanostructured Lipid Carriers

Targeting the immunosuppressive tumor microenvironment: Synergistic effect of low-dose IL12 in combination with dual immune checkpoint inhibition in a preclinical model of ovarian cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 7-7
Author(s):  
Paul G. Pavicic ◽  
Patricia A. Rayman ◽  
Hussein Al-Sudani ◽  
C. Marcela Diaz-Montero ◽  
Haider Mahdi
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Antitumor Activity ◽  
Synergistic Effect ◽  
Immune Checkpoint ◽  
Low Dose ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Activated T Cells

7 Background: Epithelial ovarian cancer (OC) is the most lethal gynecologic cancer with ~22,000 women diagnosed annually in the US. The impact of immune checkpoint inhibition (ICI) in the treatment of solid tumors has been significant. However, the response rates for OC are low ranging from 11-15%. It is critical to explore strategies to enhance the efficacy of ICI immunotherapy in OC. Targeting immunosuppressive factors and cells within the tumor microenvironment (TME) represents a feasible approach. The use of IL12 is attractive because induces potent antitumor activity by targeting myeloid cells and lymphocytes. However its clinical application has been hindered by its potential systemic toxicity. Here we explore the use of low dose intraperitoneal IL12 to enhance the antitumor activity of dual ICI in OC. Methods: Mice bearing ID8-VEGF tumors implanted intraperitoneally received either anti-PD1 alone or dual ICI treatment of anti-PD1 plus anti-CTLA4 with or without low dose IL12. Ascites accumulation was used as surrogate for tumor progression and determined by assessing weight increase. Blood and ascites were analyzed by flow cytometry for frequency of PMN-MDSC, M-MDSC, and activated T cells. Results: Low dose IL12 alone induced a significant delay in ascites accumulation when compared to untreated controls or mice treated with PD1 monotherapy or dual ICI. Addition of IL12 to dual ICI resulted in significant tumor regression and extended survival benefit compared to dual ICI alone. A synergistic effect of IL12 was not observed when combined with PD1 monotherapy. Antitumor responses associated with a marked decrease in the frequency of M-MDSC in blood and a decrease in both PMN- and M-MDSC in ascites. Decrease in MDSC associated with elevated levels of activated T cells. Conclusions: Low dose IL12 can induce regression of ID8-VEGF tumors. However, durable responses were only observed when IL12 was added to dual ICI. This suggests that IL12 can induce changes in the TME, particularly on MDSC, that can potentiate the antitumor activity of dual ICI. Our findings also suggest a crucial role of CTLA4 blockade perhaps via Treg targeting.

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