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antibody-dependent cell-mediated cytoxicity granulocyte-macrophage-colony stimulating factor month download article/chapter anti-gd2 antibody therapy li-yin lee chimeric anti-gd2 antibody antibody-dependent cytotoxicity adoptive-cell-transfer therapy targeted interleukin-2 therapy phase ib/ii trial antibody-cytokine fusion proteins lymphokine-activated killer nih grants m01-rr03186 article cancer immunology human neuroblastoma cells gd3 ganglioside full article pdf subcutaneous tumor mediated mouse monoclonal antibody renal cell cancer chimeric antidisialoganglioside antibody cell growth factor related subjects enhance tumor immunotherapy cultured autologous tumor privacy choices/manage cookies cell-mediated lysis nk cell assays shipe-spotloe jm r24 monoclonal antibody monoclonal antibody r24 il-2 therapy appeared potent antitumor response p30-ca14520 rights anti-idiotype vaccines anti-idiotype response anti-idiotypic response 5 mg/m2/day 1–10 mg/m2/day 18-il-2 fusion protein anti-gd3 phase ib trial maximal tolerated dose dose-limiting toxicities immunological effects included recombinant interleukin-2 preparations european economic area severe allergic reactions exist theoretical advantages invaded lymph node

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         headline:Phase I trial of combined treatment with ch14.18 and R24 monoclonal antibodies and interleukin-2 for patients with melanoma or sarcoma
         description: Purpose: We conducted a phase I trial of interleukin 2 (IL-2) in combination with chimeric 14.18 (ch14.18) and murine R24 antibodies to determine the maximal tolerated dose (MTD), immunological effects, and toxicity of this treatment combination. Experimental Design: Twenty-seven patients with either melanoma (23 patients) or sarcoma (4 patients) were enrolled to receive a combination therapy with ch14.18 and R24 antibodies together with continuous infusion of Roche IL-2 (1.5×106 U/m2/day, 26 patients) or Chiron IL-2 (4.5×106 U/m2/day, 1 patient) given 4 days/week for 3 weeks. The antibodies ch14.18 (2–7.5 mg/m2/day) and R24 (1–10 mg/m2/day) were scheduled to be administered for 5 days during the second week of IL-2 therapy. Results: When given in combination in this study, the MTD for ch14.18 was 5 mg/m2/day and the MTD for R24 was 5 mg/m2/day. Dose-limiting toxicities were severe allergic reactions to both ch14.18 and R24 as well as pain related to ch14.18. This ch14.18 MTD was lower than the 7.5 mg/m2/day MTD previously determined for ch14.18 given alone with the same dose and schedule of IL-2. Immunological effects included the induction of lymphokine-activated killer (LAK) activity and antibody-dependent cell-mediated cytoxicity (ADCC). Anti-idiotype response to ch14.18 was seen in six patients, including two melanoma patients who had a partial response to treatment. In addition to two partial responses, four patients had a stable disease and one patient remained without any evidence of disease. Conclusions: Immunotherapy with IL-2 in combination with ch14.18 and R24 antibodies augments LAK function and ADCC measured in vitro in all patients. While there exist theoretical advantages of combining these two antibodies, the MTD of ch14.18 and of R24 were lower than the MTD of each antibody in prior studies evaluating single antibody therapy with IL-2. As such, the combination of these two antibodies together with IL-2 therapy appeared to influence the MTD and toxicity of each of the administered antibodies.
         datePublished:2005-09-27T00:00:00Z
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            Melanoma
            Immunotherapy
            Ganglioside GD2
            Ganglioside GD3
            Antibody-dependent cell cytotoxicity
            Oncology
            Immunology
            Cancer Research
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      headline:Phase I trial of combined treatment with ch14.18 and R24 monoclonal antibodies and interleukin-2 for patients with melanoma or sarcoma
      description: Purpose: We conducted a phase I trial of interleukin 2 (IL-2) in combination with chimeric 14.18 (ch14.18) and murine R24 antibodies to determine the maximal tolerated dose (MTD), immunological effects, and toxicity of this treatment combination. Experimental Design: Twenty-seven patients with either melanoma (23 patients) or sarcoma (4 patients) were enrolled to receive a combination therapy with ch14.18 and R24 antibodies together with continuous infusion of Roche IL-2 (1.5×106 U/m2/day, 26 patients) or Chiron IL-2 (4.5×106 U/m2/day, 1 patient) given 4 days/week for 3 weeks. The antibodies ch14.18 (2–7.5 mg/m2/day) and R24 (1–10 mg/m2/day) were scheduled to be administered for 5 days during the second week of IL-2 therapy. Results: When given in combination in this study, the MTD for ch14.18 was 5 mg/m2/day and the MTD for R24 was 5 mg/m2/day. Dose-limiting toxicities were severe allergic reactions to both ch14.18 and R24 as well as pain related to ch14.18. This ch14.18 MTD was lower than the 7.5 mg/m2/day MTD previously determined for ch14.18 given alone with the same dose and schedule of IL-2. Immunological effects included the induction of lymphokine-activated killer (LAK) activity and antibody-dependent cell-mediated cytoxicity (ADCC). Anti-idiotype response to ch14.18 was seen in six patients, including two melanoma patients who had a partial response to treatment. In addition to two partial responses, four patients had a stable disease and one patient remained without any evidence of disease. Conclusions: Immunotherapy with IL-2 in combination with ch14.18 and R24 antibodies augments LAK function and ADCC measured in vitro in all patients. While there exist theoretical advantages of combining these two antibodies, the MTD of ch14.18 and of R24 were lower than the MTD of each antibody in prior studies evaluating single antibody therapy with IL-2. As such, the combination of these two antibodies together with IL-2 therapy appeared to influence the MTD and toxicity of each of the administered antibodies.
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      pageEnd:774
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      keywords:
         Melanoma
         Immunotherapy
         Ganglioside GD2
         Ganglioside GD3
         Antibody-dependent cell cytotoxicity
         Oncology
         Immunology
         Cancer Research
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