A carregar...
Publicação
CAR-T cells no tratamento do HIV
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 2.06 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
Os esforços realizados ao longo das últimas décadas aproximaram a esperança
média de vida de um indivíduo infetado com HIV à de um individuo saudável.
Os estudos da estrutura e mecanismo de replicação do vírus permitiram identificar
potenciais alvos farmacológicos e, com a descoberta dos primeiros fármacos antirretrovirais
iniciaram-se os primeiros regimes de terapêutica antirretroviral (TAR), e subsequentemente
TAR combinada.
A infeção por HIV, e potencial progressão para SIDA, tornou-se uma patologia
crónica, mas controlável, ao invés de uma doença potencialmente fatal. No entanto, as
características do vírus, nomeadamente a sua variabilidade genética e evasão ao sistema
imunitário, estabelecendo um perfil de infeção latente, tornaram as estratégias atuais
inapropriadas para o controlo desta infeção.
A tecnologia CAR-T, que combina o linfócito T com recetores quiméricos de
antigénio, representa uma alternativa promissora para o tratamento da infeção por HIV, que
permite complementar a ação das restantes estratégias, sem o risco de desenvolvimento de
resistências. Algumas das preocupações que rodeiam a utilização destas células, como a
possibilidade de síndrome de libertação de citocinas e neurotoxicidade, condicionam o seu
estudo e utilização. Contudo, estudos de índole in vitro e in vivo demonstram elevada
especificidade e reatividade seletiva para células infetadas, o que permite inferir acerca do
seu grau de segurança. Além disso, o aprofundamento do estudo desta tecnologia, e a
descoberta de novas moléculas, capazes de desempenhar funções de recetores de
superfície, concedem uma enorme versatilidade às células CAR-T e permitem ainda o
reconhecimento de novas estirpes multirresistentes de HIV.
Apesar dos seus resultados favoráveis no tratamento da infeção por HIV, a utilização
destas células a longo termo, especialmente em situações de TAR interrompida, revela ser
insuficiente, evidenciando assim a necessidade de melhorar o arsenal terapêutico contra
esta infeção.
Neste sentido, têm sido estudadas células duoCAR-T, que possuem um CAR
adicional que potencia o seu efeito terapêutico e reconhecimento de antigénios de
superfície. Através de vários estudos que comprovam o benefício acrescido da sua
utilização comparativamente às células monoCAR-T, o objetivo desta revisão é elucidar
sobre o excelente desempenho das células duoCAR-T como estratégia terapêutica para o
tratamento de indivíduos infetados com HIV.
The efforts made over the last decades brought the average life expectancy of an individual infected with HIV closer to that of an healthy individual. The study of the viral structure and replication mechanisms allowed the identification of potential pharmacological targets, and with the discovery of the first antiretroviral drugs, the first antiretroviral therapy (ART) and subsequent combined ART regimens, were initiated. HIV infection, and potential progression to AIDS, became a chronic but manageable pathology, rather than a potentially fatal disease. However, the characteristics of the virus, namely its genetic variability and immune system evasion, establishing a latent infection profile, made current strategies inappropriate for the control of this infection. CAR-T technology, that combines the T lymphocite with chimeric antigen receptors, represents a promising alternative for the treatment of HIV infection, which allows complementing other therapeutic strategies, without the risk of resistance development. Some of the concerns surrounding the use of these cells, such as the possibility of cytokine release syndrome and neurotoxicity, hamper their study and use. However, in vitro and in vivo studies demonstrate high specificity and selective reactivity for infected cells, which allows inferences about their safety level. Moreover, the further study of this technology, as well as the discovery of new molecules acting as surface receptors, provide enourmous versatility to CAR-T and also allow the recognition of new multi-resistant strains of HIV. Despite their favorable results in the treatment of HIV infection, the long-term use of these cells, especially in situations of interrupted ART, is insufficient, thus highlighting the need to improve the therapeutic arsenal against this infection. In this sense, duoCAR-T cells have been studied, which have an additional CAR that enhances their therapeutic effect and recognition of surface antigens. Through several studies that prove the added benefit of their use compared to monoCAR-T cells, the purpose of this review is to shed some light on the excellent performance of duoCAR-T cells as a therapeutic strategy for the treatment of HIV-infected individuals.
The efforts made over the last decades brought the average life expectancy of an individual infected with HIV closer to that of an healthy individual. The study of the viral structure and replication mechanisms allowed the identification of potential pharmacological targets, and with the discovery of the first antiretroviral drugs, the first antiretroviral therapy (ART) and subsequent combined ART regimens, were initiated. HIV infection, and potential progression to AIDS, became a chronic but manageable pathology, rather than a potentially fatal disease. However, the characteristics of the virus, namely its genetic variability and immune system evasion, establishing a latent infection profile, made current strategies inappropriate for the control of this infection. CAR-T technology, that combines the T lymphocite with chimeric antigen receptors, represents a promising alternative for the treatment of HIV infection, which allows complementing other therapeutic strategies, without the risk of resistance development. Some of the concerns surrounding the use of these cells, such as the possibility of cytokine release syndrome and neurotoxicity, hamper their study and use. However, in vitro and in vivo studies demonstrate high specificity and selective reactivity for infected cells, which allows inferences about their safety level. Moreover, the further study of this technology, as well as the discovery of new molecules acting as surface receptors, provide enourmous versatility to CAR-T and also allow the recognition of new multi-resistant strains of HIV. Despite their favorable results in the treatment of HIV infection, the long-term use of these cells, especially in situations of interrupted ART, is insufficient, thus highlighting the need to improve the therapeutic arsenal against this infection. In this sense, duoCAR-T cells have been studied, which have an additional CAR that enhances their therapeutic effect and recognition of surface antigens. Through several studies that prove the added benefit of their use compared to monoCAR-T cells, the purpose of this review is to shed some light on the excellent performance of duoCAR-T cells as a therapeutic strategy for the treatment of HIV-infected individuals.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
HIV CAR-T duoCAR-T TAR Mestrado integrado - 2021