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Cancer Res ; 52(11): 3005-10, 1992 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-1591717

RESUMEN

We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.


Asunto(s)
Carboximetilcelulosa de Sodio/toxicidad , Interleucina-2/toxicidad , Neoplasias/terapia , Poli I-C/toxicidad , Polilisina/toxicidad , Antígenos CD/análisis , Biopterinas/análogos & derivados , Biopterinas/sangre , Carboximetilcelulosa de Sodio/uso terapéutico , Citotoxicidad Inmunológica , Evaluación de Medicamentos , Femenino , Humanos , Interleucina-2/uso terapéutico , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neopterin , Poli I-C/uso terapéutico , Polilisina/uso terapéutico
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