Strategies to Enhance the Therapeutic Efficacy, Applicability, and Safety of Genetically Engineered Immune Cells

Autor(es)

Gomes de Lima, Sarah Caroline ; Carvalho Fantacini, Daianne Maciely ; Batista, Lais de Castro ; Silveira, Roberta Maraninchi ; Furtado, Izadora Peter ; Rossetti, Rafaela ; Brand, Heloisa ; Covas, Dimas Tadeu ; Botelho de Souza, Lucas Eduardo

• Tipo de documento: Artigo Científico
• Fonte: CRITICAL REVIEWS IN IMMUNOLOGY; v. 41, n. 1, p. 27-pg., 2021-01-01.

Resumo

The field of cell therapy is leading a paradigm shift in drug development. The recent convergence of several fields, including immunology, genetics, and synthetic biology, now allows for the introduction of artificial receptors and the design of entire genetic circuitries to finely program the behavior of injected cells. A prime example of these next-generation living drugs comes in the form of T cells expressing chimeric antigen receptors (CARs), which have already demonstrated definitive evidence of therapeutic efficacy against some hematological malignancies. However, several obstacles still restrict the antitumor efficacy of and impair the widespread use of CAR-T cells. Critical challenges include limited persistence and antitumor activity in vivo, antigen escape, scarcity of suitable single markers for targeting, and therapy-related toxicity. Nevertheless, intense research activity in this field has resulted in a plethora of creative solutions to address each of these limitations. In this review, we provide a comprehensive snapshot of the current strategies used to enhance the therapeutic efficacy, applicability, and safety of genetically engineered immune cells to treat cancer. (AU)

• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 20/02043-2 - Estabelecimento de uma metodologia de edição gênica por CRISPR/Cas9 para a geração de linfócitos T-CAR alogênicos prontos para o uso
• Beneficiário: Sarah Caroline Gomes de Lima
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 19/18702-8 - Geração e avaliação da eficiência antitumoral de linfócitos T CAR com fenótipo T helper 17
• Beneficiário: Heloisa Brand
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 19/18672-1 - Avaliação da persistência in vivo de linfócitos T expressando receptores de antígeno quiméricos anti-CD19
• Beneficiário: Laís de Castro Batista
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica