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Cancer Res ; 45(3): 1058-65, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3155990


In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.

Adyuvantes Inmunológicos/farmacología , Carboximetilcelulosa de Sodio/farmacología , Inductores de Interferón/farmacología , Metilcelulosa/análogos & derivados , Péptidos/farmacología , Poli I-C/farmacología , Polilisina/farmacología , Animales , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Prueba de Cultivo Mixto de Linfocitos , Activación de Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Linfocitos T/efectos de los fármacos
Cancer Res ; 45(3): 1066-72, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3971361


The systemic administration of multiple, nontoxic doses of polyinosinic-polycytidylic acid and poly-L-lysine solubilized by carboxymethylcellulose [poly(I,C)-LC] eradicated established experimental and spontaneous pulmonary metastases. Optimal immunotherapy was schedule dependent, requiring three to five injections of poly(I,C)-LC per week for a minimum of 4 weeks; in addition, therapeutic efficiency was partially dosage independent. Immunotherapy by poly(I,C)-LC was found to be limited by tumor burden, although when combined with chemotherapy as a debulking regimen it resulted in increased survival with protocols in which poly(I,C)-LC alone was insufficient. These data suggest that the systemic administration of poly(I,C)-LC may provide a successful adjuvant therapeutic modality against cancer metastasis.

Adyuvantes Inmunológicos/uso terapéutico , Carboximetilcelulosa de Sodio/uso terapéutico , Inductores de Interferón/uso terapéutico , Metilcelulosa/análogos & derivados , Neoplasias Experimentales/tratamiento farmacológico , Péptidos/uso terapéutico , Poli I-C/uso terapéutico , Polilisina/uso terapéutico , Animales , Carboximetilcelulosa de Sodio/administración & dosificación , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Inmunoterapia , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Poli I-C/administración & dosificación , Polilisina/administración & dosificación