caa a22 4500 469073667 CHVBK 20180323132928.0 cr unu---uuuuu 170328e19920501xx s 000 0 eng 10.1007/BF01756181 doi (NATIONALLICENCE)springer-10.1007/BF01756181 Antitumor effects of interleukin-2 and mismatched double-stranded RNA, individually and in combination, against a human malignant melanoma xenograft [Elektronische Daten] [Howard Hubbell, Hugo Vargas, Karen Tsujimoto, George Gibson, Edward Pequignot, Robert Bigler, William Carter, David Strayer] Summary: The antitumor effects of recombinant interleukin-2 (rIL-2) and mismatched double-stranded RNA (dsRNA) were assessed in tissue culture and in a nude mouse model. Mismatched dsRNA did not show a direct antiproliferative effect against the human malignant melanoma cell line, BRO, in tissue culture. However, treatment of the BRO cells with up to 1000 units/ml rIL-2 in culture showed a slight increase in growth rate. Combined rIL-2/mismatched dsRNA treatment also demonstrated a similar slight enhancement of growth. Nude mice bearing subcutaneous tumors were treated by intraperitoneal injection of low doses (5000-20 000 units) of rIL-2 and mismatched dsRNA (500 µg). The in vivo tumor growth was significantly inhibited by the combined treatments (P <0.05) and survival was significantly increased (P <0.05). Measurement of cytotoxicity using splenocytes from treated animals showed significant augmentation of lytic activity against natural killer(NK)-sensitive YAC-1 cells in all rIL-2/mismatched dsRNA treatment groups, compared to the individual treatments or controls (P <0.05). Cytotoxicity of the splenocytes against the NK-resistant BRO cells was also augmented in animals treated with mismatched dsRNA and the highest rIL-2 dose utilized here (P <0.01). Renal, liver, and hematological toxicity was evaluated by measurement of blood urea nitrogen, creatinine, serum asparrtate aminotransferase, and a complete blood count with differential. There were no significant differences in these parameters in any of the treatment groups. Similarly, no differences in weight of the animals was seen in any treatment group. These results indicate that the combination of low-dose rIL-2 and mismatched dsRNA can potentiate host-mediated antitumor effects, yielding increased survival, without significant toxicity. Springer-Verlag, 1992 Interleukin-2 nationallicence Mismatched dsRNA nationallicence Lymphokine-activated killer cells nationallicence Antitumor effects nationallicence Human melanoma xenografts nationallicence Hubbell Howard Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Vargas Hugo Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Tsujimoto Karen Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Gibson George Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Pequignot Edward Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Bigler Robert Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Carter William Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Strayer David Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut Cancer Immunology, Immunotherapy Springer-Verlag 35/3(1992-05-01), 151-157 0340-7004 35:3<151 1992 35 262 https://doi.org/10.1007/BF01756181 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01756181 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hubbell Howard Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Vargas Hugo Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Tsujimoto Karen Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Gibson George Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Pequignot Edward Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Bigler Robert Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Carter William Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 700 1- Strayer David Department of Neoplastic Diseases, Hahnemann University, Broad and Vine, 19102, Philadelphia, Pennsylvania, USA aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/3(1992-05-01), 151-157 0340-7004 35:3<151 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer