Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts Bryce D Beseth, MD, Robert B Cameron, MD, Pamela Leland,

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Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts Bryce D Beseth, MD, Robert B Cameron, MD, Pamela Leland, Liang You, MD, PhD, Frederick Varricchio, MD, PhD, Robert J Kreitman, MD, Richard A Maki, PhD, David M Jablons, MD, Syed R Husain, PhD, Raj K Puri, MD, PhD The Annals of Thoracic Surgery Volume 78, Issue 2, Pages 436-443 (August 2004) DOI: 10.1016/j.athoracsur.2004.03.010

Fig 1 (A) Binding displacement of 125I-labeled interleukin-4 (IL-4) by unlabeled IL-4. (B) Binding displacement of 125I-labeled IL-4 by unlabeled IL-4 (▴) or IL-13 (■). (CPM = counts per minute.) The Annals of Thoracic Surgery 2004 78, 436-443DOI: (10.1016/j.athoracsur.2004.03.010)

Fig 2 Interleukin-4 receptor (IL-4R) detection in mesothelioma tissues by immunohistochemical analysis. Left upper panel: Mouse immunoglobulin G (IgG) as isotype control (×40). Left lower panel: no secondary antibody (×40). Right upper panel: Anti-IL-4R monoclonal antibody (M-57) (×40). Right lower panel: Anti-IL-4R monoclonal antibody (M-57) and Vector NovaRed stain (×60). The Annals of Thoracic Surgery 2004 78, 436-443DOI: (10.1016/j.athoracsur.2004.03.010)

Fig 3 (A) Comparison of protein synthesis inhibition mediated by cpIL-4-PE on mesothelioma cell lines MS-1 (▴) and MSTO-211H (■). Mesothelioma cells were cultured with various concentrations of cpIL-4-PE and protein synthesis was measured by 3H-leucine incorporation after 20 hours of culture. The results are presented as the mean percentage of control of untreated cells from triplicate determinations. (B) The mesothelioma cell line MS-1 was cultured with various concentrations of cpIL-4-PE with (■) or without (▴) an excess of IL-4. Protein synthesis was measured after 20 hours of culture by incorporation of 3H-leucine. The results are presented as the mean percentage of control of untreated cells from triplicate determinations. (IL = interleukin.) The Annals of Thoracic Surgery 2004 78, 436-443DOI: (10.1016/j.athoracsur.2004.03.010)

Fig 4 In vivo antitumor activity of cpIL-4-PE against mesothelioma tumors in nude mice. Nude mice were inoculated with 5 × 106 Meso-1 cells on day 0 and then treated with intratumoral injections of low-dose cpIL-4-PE (♦), high-dose cpIL-4-PE(■), interleukin (IL)-4 control (•), or vehicle control (▴) only. The data presented are the mean ± SE of the 5 animals in each group. The Annals of Thoracic Surgery 2004 78, 436-443DOI: (10.1016/j.athoracsur.2004.03.010)

Fig 5 Survival of mice after intratumoral treatment of human mesothelioma xenografts. Groups of 5 mice were inoculated with 5 × 106 Meso-1 cells and then treated with intratumoral injections of interleukin-4 control (——), low-dose cpIL-4-PE (), high-dose toxin (——), or vehicle control (----). The mice were then followed for survival for up to 104 days. The Annals of Thoracic Surgery 2004 78, 436-443DOI: (10.1016/j.athoracsur.2004.03.010)