Andrew Zloza

Carl E Ruby

Erica J Huelsmann

Howard L Kaufman

Joseph L Poshepny

Joseph R Broucek

Tasha Hughes

Journal for ImmunoTherapy of Cancer

PubMed

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POSTER PRESENTATION Open AccessCombination immunotherapy with Interleukin-2and CTLA-4 blockade decreases tumorgrowth and improves overall survivalJoseph R Broucek1*, Tasha Hughes1, Erica J Huelsmann2, Joseph L Poshepny2, Carl E Ruby1,2, Andrew Zloza2,3,Howard L Kaufman1,2,3From Society for Immunotherapy of Cancer 28th Annual MeetingNational Harbor, MD, USA. 8-10 November 2013BackgroundCombination immunotherapy is quickly gaining attentionin the field of cancer treatment. IL-2, a cytokine whichactivates T cells, and ipilimumab, a monoclonal antibodythat blocks CTLA-4, are both approved as monotherapyfor metastatic melanoma. To date, combination immu-notherapy with IL-2 and anti-CTLA-4 has not beenadequately investigated. We hypothesized that that thiscombination may work synergistically owing to its dis-tinct but complementary mechanisms of T cell activation.MethodsC57BL/6 mice (10 per group) were challenged withB16-F10 melanoma (via intradermal injection with 120,000cells) on day 0. Four groups were treated via intraperitonealinjection: -Group 1 (combination): IL-2 (100,000 units in100 µl) every 12 h on days 4-8 and anti-CTLA-4 (100 µg in100 µl) on days 3, 6, and 9; -Group 2 (IL-2 only): IL-2(100,000 units in 100 µl) every 12 h on days 4-8 and IgG(100 µg in 100 µl) on days 3, 6, and 9; -Group 3 (anti-CTLA-4 only): PBS (100 µl) every 12 h on days 4-8 andanti-CTLA-4 (100 µg in 100µl) on days 3, 6, and 9; -Group4 (placebo): PBS (100 µl) every 12 h on days 4-8 and IgG(100 µg in 100 µl) on days 3, 6, and 9. Tumor area(length*width) was measured every other day until death ofthe animal or until tumors reached 100mm2, when animalswere sacrificed as per institutional protocols. Primary out-comes included tumor size and overall survival.ResultsTumor growth was significantly reduced with combina-tion IL-2 and anti-CTLA-4. Specifically, on day 14, themean tumor area with combination IL-2 and anti-CTLA-4 was 2mm2, while in the anti-CTLA-4 only, IL-2 only,and placebo groups it was 14, 29, and 68 mm2, respec-tively (P<0.01 for all comparisons, except IL-2 only ver-sus anti-CTLA-4 only [not significant]). At day 30, theoverall survival with combination IL-2 and anti-CTLA-4was 50%, while with IL-2 only and anti-CTLA-4 only itwas 10% and 20%, respectively (P<0.01 for all compari-sons). All animals treated in the placebo group suc-cumbed to their tumors by day 19. These findings wereconfirmed in a second experiment with similar results.ConclusionsCombination immunotherapy with IL-2 activation andCTLA-4 blockade significantly decreases tumor growthand increases overall survival when compared to IL-2 oranti-CTLA-4 monotherapy or placebo. The role of CD8+effector versus CD4+ regulatory T cells in the success ofthis immunotherapy is ongoing and will be included inour formal presentation. Ultimately, we aim to translatethis work into a combination immunotherapy clinical trial.Authors’ details1Department of Surgery, Rush University Medical Center, Chicago, IL, USA.2Department of Immunology/Microbiology, Rush University Medical Center,Chicago, IL, USA. 3Department of Internal Medicine, Rush University MedicalCenter, Chicago, IL, USA.Published: 7 November 2013doi:10.1186/2051-1426-1-S1-P70Cite this article as: Broucek et al.: Combination immunotherapy withInterleukin-2 and CTLA-4 blockade decreases tumor growth andimproves overall survival. Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P70.1Department of Surgery, Rush University Medical Center, Chicago, IL, USAFull list of author information is available at the end of the articleBroucek et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P70http://www.immunotherapyofcancer.org/content/1/S1/P70© 2013 Broucek et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

Combination immunotherapy with Interleukin-2 and CTLA-4 blockade decreases tumor growth and improves overall survival

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Combination immunotherapy with Interleukin-2 and CTLA-4 blockade decreases tumor growth and improves overall survival

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