RESUMO
HIV protease inhibitors have been shown to exert antiangiogenic and antitumor actions independently from their antiretroviral effect. Based on these studies, HIV-seronegative patients with classic Kaposi's sarcoma were treated with indinavir and followed for clinical evolution, drug pharmacokinetics and Kaposi's sarcoma biomarkers. A favorable clinical course was associated with high drug plasma levels, reduced production of basic fibroblast growth factor, lower numbers of circulating endothelial cells, and a decrease in antibody titers against human herpesvirus 8.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Indinavir/uso terapêutico , Sarcoma de Kaposi/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Antineoplásicos/sangue , Biomarcadores Tumorais/sangue , Inibidores da Protease de HIV/sangue , Soronegatividade para HIV , Herpesvirus Humano 8/imunologia , Humanos , Indinavir/sangue , Pessoa de Meia-Idade , Sarcoma de Kaposi/sangue , Resultado do TratamentoRESUMO
A cDNA vaccine (pVax1/pet-neu) was designed to encode 12 different Her-2/ErbB-2-derived, HLA-A*0201-restricted dominant and high-affinity heteroclitic cryptic epitopes. Vaccination with pVax1/pet-neu triggered multiple and ErbB-2-specific CTL responses in HLA-A*0201 transgenic HHD mice and in HLA-A*0201 healthy donors in vitro. Human and murine CTL specific for each one of the 12 ErbB-2 peptides recognized in vitro both human and murine tumor cells overexpressing endogenous ErbB-2. Furthermore, vaccination of HHD mice with pVax1/pet-neu significantly delayed the in vivo growth of challenged ErbB-2-expressing tumor (EL4/HHD/neu murine thymoma) more actively when compared with vaccination with the empty vector (pVax1) or vehicle alone. These data indicate that the pVax1/pet-neu cDNA vaccine coding for a poly-ErbB-2 epitope is able to generate simultaneous ErbB-2-specific antitumor responses against dominant and cryptic multiple epitopes.
