RESUMO
R24 is an IgG3 mouse monoclonal antibody which recognizes the ganglioside GD3. Two variants of R24, in which one (V2-R24) or both (V1-R24) light chains were substituted by MOPC-21 light chains, were isolated and characterized. R24 had a 40-fold higher avidity for GD3 than either variant, suggesting that high avidity binding required the presence of two R24 light chains and, thus, divalency. R24 and both variants mediated antibody-dependent cellular cytotoxicity but antibody-dependent cellular cytotoxicity mediated by variants was weak compared to R24. The presence of at least one R24 light chain was required for complement-dependent cytotoxicity; complement-dependent cytotoxicity was mediated by R24 and weakly by V2-R24 but not by V1-R24. R24, but not V1-R24 or V2-R24, inhibited attachment of melanoma cells to plastic and activated T-lymphocytes, suggesting a threshold of avidity required for these biological effects. In a human melanoma xenograft model in nu/nu mice, radiolabeled R24, variants, and isotype-matched control monoclonal antibodies all appeared to localize in tumors (based on tumor:normal tissue ratios), but specific tumor targeting by R24 was generally 3- to 6-fold higher. R24 prevented melanoma outgrowth in nu/nu mice, while V2-R24 induced partial tumor protection. V1-R24 and the negative control monoclonal antibody did not inhibit tumor outgrowth. Antitumor activity of R24 corresponded to avidity and ability to mediate complement-dependent cytotoxicity in vitro.
Assuntos
Anticorpos Monoclonais/análise , Afinidade de Anticorpos/imunologia , Gangliosídeos/imunologia , Imunoglobulina G/análise , Cadeias Leves de Imunoglobulina/análise , Melanoma/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacocinética , Citotoxicidade Celular Dependente de Anticorpos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/farmacocinética , Cadeias Leves de Imunoglobulina/imunologia , Ativação Linfocitária , Melanoma/prevenção & controle , Camundongos , Peso Molecular , Transplante de Neoplasias , Células Tumorais Cultivadas/imunologiaAssuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Gangliosídeos/imunologia , Melanoma/secundário , Animais , Ensaios Clínicos como Assunto , Citotoxicidade Imunológica , Humanos , Imunização , Imunoglobulina G/imunologia , Idiótipos de Imunoglobulinas/imunologia , Melanoma/terapia , Camundongos , Linfócitos T/imunologiaRESUMO
A prospective clinical trial of concomitant interferon-alpha 2b and etoposide was conducted in 24 previously untreated patients with epidemic Kaposi's sarcoma. Eight of 21 evaluable patients (38%) achieved either a complete response (1 patient) or a partial response (7 patients). None of the responders had a prior history of opportunistic infection. Hematologic toxicity was severe, and 8 patients developed an opportunistic infection. The combination of interferon-alpha 2b and etoposide has modest activity, but no additive or synergistic activity was evident in the dose and schedule utilized in this study. The exact role for interferon-alpha in epidemic Kaposi's sarcoma, both as a single agent and in combinations, remains to be determined.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Etoposídeo/uso terapêutico , Interferon Tipo I/uso terapêutico , Interferon-alfa/uso terapêutico , Sarcoma de Kaposi/terapia , Adulto , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Sarcoma de Kaposi/etiologiaRESUMO
Mucocutaneous lesions are often a prominent manifestation of the acquired immune deficiency syndrome (AIDS). Patients with this syndrome are susceptible to a number of opportunistic skin infections as well as an aggressive form of Kaposi's sarcoma. The diagnosis, the clinical setting, and the treatment of these diseases are discussed.