RESUMEN
Introduction: Outcomes of patients with classical Hodgkin lymphoma are excellent, and the intent of frontline therapy for even advanced-stage disease has been curative. This review summarizes the role of brentuximab vedotin in the upfront treatment of advanced stage classical Hodgkin lymphoma in the context of reducing therapy-related toxicity without compromising the high cure rate. Areas covered: Strategies to reduce bleomycin-induced lung toxicity include a response-adapted approach investigated in the RATHL study and a replacement of bleomycin with brentuximab vedotin in frontline chemotherapy regimens. In both studies, omission of bleomycin in the non-standard arms decreased the rate of pulmonary toxicity while maintaining high progression-free survival and overall survival rates. Expert opinion: The approval of A+AVD in North America offers a new bleomycin-free regimen for the treatment of advanced-stage HL, but it must be balanced against a risk-adapted approach. Recently presented subset analyses raise a question about which patients benefit most from this therapy.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Inmunotoxinas/uso terapéutico , Antineoplásicos Inmunológicos/economía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversos , Bleomicina/economía , Brentuximab Vedotina/economía , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Dacarbazina/economía , Dacarbazina/uso terapéutico , Doxorrubicina/economía , Doxorrubicina/uso terapéutico , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/economía , Enfermedad de Hodgkin/mortalidad , Humanos , Inmunotoxinas/economía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Análisis de Supervivencia , Vinblastina/economía , Vinblastina/uso terapéuticoAsunto(s)
Anticuerpos/uso terapéutico , Ensayos Clínicos como Asunto , Diseño de Fármacos , Drogas en Investigación/uso terapéutico , Anticuerpos/química , Anticuerpos/economía , Anticuerpos/metabolismo , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/uso terapéutico , Especificidad de Anticuerpos , Antineoplásicos/química , Antineoplásicos/economía , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Costos de los Medicamentos , Drogas en Investigación/química , Drogas en Investigación/economía , Drogas en Investigación/metabolismo , Humanos , Inmunotoxinas/química , Inmunotoxinas/economía , Inmunotoxinas/metabolismo , Inmunotoxinas/uso terapéutico , Ligandos , Neoplasias/tratamiento farmacológico , Neoplasias/economía , Ingeniería de ProteínasRESUMEN
Full-length antibodies and antibodies that ferry a cargo to target cells are desired biopharmaceuticals. We describe the production of full-length IgGs and IgG-toxin fusion proteins in E. coli. In the presented examples of anti CD30 and anti EGF-receptor antibodies, the antibody heavy and light chains or toxin fusions thereof were expressed in separate bacterial cultures, where they accumulated as insoluble inclusion bodies. Following refolding and purification, high yields (up to 50 mg/L of shake flask culture) of highly purified (>90%) full-length antibodies and antibody-toxin fusions were obtained. The bacterially produced antibodies, named "Inclonals," equaled the performance of the same IgGs that were produced using conventional mammalian cell culture in binding properties as well as in cell killing potency. The rapid and cost effective IgG production process and the high quality of the resultant product may make the bacterial production of full-length IgG and IgG-drug fusion proteins an attractive option for antibody production and a significant contribution to recombinant antibody technology.