Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
 4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.
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PMID:Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma. 216 55

In a phase I trial the toxicity and immunomodulatory effects of combined treatment with intravenous (i.v.) bispecific monoclonal antibody BIS-1 and subcutaneous (s.c.) interleukin 2 (IL-2) was studied in renal cell cancer patients. BIS-1 combines a specificity against CD3 on T lymphocytes with a specificity against a 40 kDa pancarcinoma-associated antigen, EGP-2. Patients received BIS-1 F(ab')2 fragments intravenously at doses of 1, 3 and 5 micrograms kg-1 body weight during a concomitantly given standard s.c. IL-2 treatment. For each dose, four patients were treated with a 2 h BIS-1 infusion in the second and fourth week of IL-2 therapy. Acute BIS-1 F(ab')2-related toxicity with symptoms of chills, peripheral vasoconstriction and temporary dyspnoea was observed in 2/4 and 5/5 patients at the 3 and 5 micrograms kg-1 dose level respectively. The maximum tolerated dose (MTD) of BIS-1 F(ab')2 was 5 micrograms kg-1. Elevated plasma levels of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were detected at the MTD. Flow cytometric analysis showed a dose-dependent binding of BIS-1 F(ab')2 to circulating T lymphocytes. Peripheral blood mononuclear cells (PBMCs), isolated after treatment with 3 and 5 micrograms kg-1 BIS-1, showed increased specific cytolytic capacity against EGP-2+ tumour cells as tested in an ex vivo performed assay. Maximal killing capacity of the PBMCs, as assessed by adding excess BIS-1 to the assay, was shown to be decreased after BIS-1 infusion at 5 micrograms kg-1 BIS-1 F(ab')2. A BIS-1 F(ab')2 dose-dependent disappearance of circulating mononuclear cells from the peripheral blood was observed. Within the circulating CD3+ CD8+ lymphocyte population. LFA-1 alpha-bright and HLA-DR+ T-cell numbers decreased preferentially. It is concluded that i.v. BIS-1 F(ab')2, when combined with s.c. IL-2, has a MTD of 5 micrograms kg-1. The treatment endows the T lymphocytes with a specific anti-EGP-2-directed cytotoxic potential.
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PMID:Phase I study of intravenously applied bispecific antibody in renal cell cancer patients receiving subcutaneous interleukin 2. 791 12

Bispecific antibody HEA125 x OKT3 was shown to redirect T lymphocytes toward carcinoma cells and to induce tumor cell lysis in vitro. Preclinical studies have demonstrated that tumor-associated lymphocytes (TAL) derived from malignant ascites can be used as effector cells with a high efficacy and without prior stimulation. These data provided the rationale for a clinical trial to investigate whether bsAb HEA125 x OKT3 is also able to induce tumor cell lysis in vivo and can be used for local treatment of malignant ascites arising from ovarian carcinoma. Ten ovarian carcinoma patients presenting with malignant ascites resistant to chemotherapy were enrolled in the study. They received weekly intraperitoneal injections of 1 mg bsAb diluted in 500 ml NaCl solution to allow homogeneous antibody distribution within the peritoneal cavity. All patients responded clinically well to the therapy. Eight patients experienced a complete and 2 patients a partial reduction of ascites production. A decrease or stabilization of tumor marker CA125 was detected in the sera of 8 patients. Only WHO Grade I and II toxicity was observed including mild fever, chills and allergic eczema. Thus, intraperitoneal application of bsAb HEA125 x OKT3 appears to be an easy and cost effective palliative treatment for ovarian carcinoma with recurrent ascites that leads to a substantially increased quality of life for the patients. During therapy TNF-alpha concentrations raised markedly in the ascites fluid whereas VEGF and sFLT-1 ascites levels declined. This indicates that not only T cell-mediated tumor cell lysis but also changes in vascular permeability due to downregulation of VEGF and its receptors might be responsible for the beneficial therapeutic effect.
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PMID:Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma. 1220 96