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Publication
Terapia Celular: células CAR-T
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Advisor(s)
Abstract(s)
A terapia com células CAR-T consiste na modificação genética de células T autólogas para expressarem à sua superfície um recetor antigénico quimérico que irá ser direcionado para um antigénio alvo, resultando na eliminação do tumor devido à atividade citotóxica das células T. Atualmente existem mais de 500 ensaios clínicos a decorrer em todo o mundo em que o objeto de estudo são as células CAR-T para o tratamento de tanto tumores hematológicos como para tumores sólidos que têm demonstrado resultados altamente promissores. Destes ensaios clínicos resultaram a aprovação de 5 produtos utilizando esta tecnologia, desses 5, apenas 3 estão, até ao momento, aprovados na Europa.
Existem 4 gerações de células CAR-T, sendo que, os medicamentos aprovados todos são pertencentes à segunda geração. No entanto, a evolução das gerações está linearmente relacionada com o aumento da eficácia desta terapêutica.
Porém, existem limitações inerentes a esta terapia, tanto a nível do processo de produção como a nível de toxicidade, sendo por isso, muito importante a investigação contínua nesta área. Por enquanto, a produção é um processo demorado e tem um elevado custo associado. Relativamente à toxicidade, esta terapia está associada a efeitos adversos graves como é o caso da síndrome de libertação de citocinas e a neurotoxicidade, sendo imperativo aumentar o seu perfil de segurança. Contudo, existem estratégias que têm como objetivo aumentar a segurança da utilização desta terapia.
Até ao momento, os fármacos desenvolvidos e aprovados apenas são indicados para tumores hematológicos, tendo vindo a demonstrar resultados notáveis. Porém, os resultados dos ensaios clínicos para os tumores sólidos não são tão promissores, uma vez que as células CAR-T estão sujeitas a uma série de obstáculos para encontrar, entrar e sobreviver no tumor e tornar esta terapia eficaz.
Esta terapia tem um mundo de possibilidades relativamente às suas perspetivas no futuro, destacando-se o sistema de células SUPRA CAR, as células CAR-NK e ainda a terapia “off-the-shelf”.
A introdução no mercado destas terapias é avaliada pelas agências regulamentares do medicamento por um processo acelerado de modo a disponibilizá-la rapidamente a quem necessita, sendo rigorosamente monitorizada após a sua aprovação.
Therapy with CAR-T cells consists of the genetic modification of autologous T cells to express on their surface a chimeric antigenic receptor that will be directed to a target antigen, resulting in the elimination of the tumor due to the cytotoxic activity of the T cells. Currently, there are more than 500 clinical trials underway in the world in which the object of study is CAR-T cells for the treatment of hematological tumors and solid tumors, which have shown highly promising results. These clinical trials resulted in the approval of 5 products using this technology, of these 5, only 3 are approved in Europe. There are 4 generations of CAR-T cells, and the approved drugs all belong to the second generation. However, the evolution of generations is linearly related to the increase in the effectiveness of this therapy. However, there are limitations inherent to this therapy, both in terms of the production process and in terms of toxicity, which is why continuous research in this area is very important. For now, production is a time-consuming process and has a high associated cost. Regarding toxicity, this therapy is associated with serious adverse effects such as cytokine release syndrome and neurotoxicity, and it is imperative to increase its safety profile. However, there are strategies that aim to increase the safety of using this therapy. So far, the drugs developed and approved are only indicated for hematological tumors, having been showing remarkable results. However, clinical trial results for solid tumors are not as promising, as CAR-T cells are subject to several obstacles to finding, entering and surviving in the tumor and making this therapy effective. This therapy has a world of possibilities for its future, highlighting the SUPRA CAR cell system, the CAR-NK cells and even the “off-the-shelf” therapy. The market introduction of these therapies is evaluated by the medicine’s agencies through an accelerated process in order to make it available quickly to those who need it, and it is strictly monitored after its approval.
Therapy with CAR-T cells consists of the genetic modification of autologous T cells to express on their surface a chimeric antigenic receptor that will be directed to a target antigen, resulting in the elimination of the tumor due to the cytotoxic activity of the T cells. Currently, there are more than 500 clinical trials underway in the world in which the object of study is CAR-T cells for the treatment of hematological tumors and solid tumors, which have shown highly promising results. These clinical trials resulted in the approval of 5 products using this technology, of these 5, only 3 are approved in Europe. There are 4 generations of CAR-T cells, and the approved drugs all belong to the second generation. However, the evolution of generations is linearly related to the increase in the effectiveness of this therapy. However, there are limitations inherent to this therapy, both in terms of the production process and in terms of toxicity, which is why continuous research in this area is very important. For now, production is a time-consuming process and has a high associated cost. Regarding toxicity, this therapy is associated with serious adverse effects such as cytokine release syndrome and neurotoxicity, and it is imperative to increase its safety profile. However, there are strategies that aim to increase the safety of using this therapy. So far, the drugs developed and approved are only indicated for hematological tumors, having been showing remarkable results. However, clinical trial results for solid tumors are not as promising, as CAR-T cells are subject to several obstacles to finding, entering and surviving in the tumor and making this therapy effective. This therapy has a world of possibilities for its future, highlighting the SUPRA CAR cell system, the CAR-NK cells and even the “off-the-shelf” therapy. The market introduction of these therapies is evaluated by the medicine’s agencies through an accelerated process in order to make it available quickly to those who need it, and it is strictly monitored after its approval.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
CAR-T Imunoterapia Tumores hematológicos Tumores sólidos Mestrado integrado - 2021