1. The Immunocytokine L19–IL2 Eradicates Cancer When Used in Combination with CTLA-4 Blockade or with L19-TNF 
Kathrin Schwager, Teresa Hemmerle, David Aebischer, Dario Neri 
Journal of Investigative Dermatology 
Volume 133, Issue 3, Pages (March 2013)
DOI: /jid
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2. Figure 1
Characterization of immunocytokines and tumors. (a) Schematic representation of the two immunocytokines L19–IL2 and L19-TNF. L19–IL2 has a dimeric structure, whereas L19-TNF forms noncovalent trimers through the trimerization of tumor necrosis factor (TNF). (b) Immunhistochemical evaluation of extra-domain B (EDB) expression in the CT26 murine colon carcinoma and the F9 murine teratocarcinoma. Immunohistochemistry using the antibody L19 revealed a strong expression of EDB fibronectin in both tumors. Bar=100μm.
Journal of Investigative Dermatology  , DOI: ( /jid )
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3. Figure 2
Therapeutic activity of L19–IL2 and anti-CTLA-4 in monotherapy and combination therapy against established subcutaneous murine F9 teratocarcinoma. (a) Tumor growth curve. Treatment was stared at day 6 after tumor cell implantation, and mice received intravenous injections of 30μg L19–IL2, 50μg anti-CTLA-4, and a combination of 30μg L19–IL2 and 50μg anti-CLTA-4. Phosphate-buffered saline (PBS) was used as a vehicle. Treatment was repeated after 4 days. Data represent mean(±SEM) tumor volumes; n=5 mice per group. (b) Data are graphed as the Kaplan–Meier survival curve. The addition of L19–IL2 to anti-CTLA-4 resulted in 20–40% survival, whereas all animals treated with the single agent L19–IL2 or anti-CLTA-4 died within 3 weeks.
Journal of Investigative Dermatology  , DOI: ( /jid )
Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

4. Figure 3
Therapeutic activity of L19–IL2 and anti-CTLA-4 in monotherapy and combination therapy against CT26 colon carcinoma. (a) Treatment was started when tumors reached a size of 70mm3, and mice received intravenous (i.v.) injections on days 5, 8, and 11 after tumor implantation of either 30μg L19–IL2 (▴), 50μg anti-CTLA-4 (□), 30μg L19–IL2, followed by 50μg anti-CLTA-4 24hours later (x), 50μg anti-CTLA-4, followed by 30μg L19–IL2 24hours later (•), or phosphate-buffered saline (PBS; ♦) as a control. (b) Treatment was started when tumors reached a size of 150mm3 and mice received i.v. injection on days 8, 11, and 14 after tumor implantation. Dose and treatment schedule were identical to the one in a.
Journal of Investigative Dermatology  , DOI: ( /jid )
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5. Figure 4
Cytokine analysis in tumor extracts using multiplexed bead-based flow cytometry.
Journal of Investigative Dermatology  , DOI: ( /jid )
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6. Figure 5
Ex vivo immunofluorescence analysis of tumor-infiltrating cells on tumor section following treatment. PBS, phosphate-buffered saline. Bar=100μm.
Journal of Investigative Dermatology  , DOI: ( /jid )
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7. Figure 6
Therapeutic activity of intratumoral L19–IL2, L19-TNF, and the combination. (a) Established subcutaneous F9 teratocarcinomas were injected intratumorally on day 7 with L19–IL2 (▴), L19-TNF (□), the combination (x), or phosphate-buffered saline (PBS; ♦). Data represent mean tumor volumes (±SEM); n≥5 mice per group. (b) F9 tumors of different sizes were injected intratumorally with 30μg L19–IL2 and 7μg L19-TNF. Data represent mean tumor volumes (±SEM); n≥5 mice per group. (c) Treatment of subcutaneously grafted F9 tumors on athymic mice compared with immunocompetent mice with a single intratumoral injection of 30μg L19–IL2 and 7μg L19-TNF. Data represent mean tumor volumes (±SEM); n≥4 mice per group. CR, complete response.
Journal of Investigative Dermatology  , DOI: ( /jid )
Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions