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

Author(s)

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

• Document type: Journal article
• Source: CRITICAL REVIEWS IN IMMUNOLOGY; v. 41, n. 1, p. 27-pg., 2021-01-01.

Abstract

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)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/02043-2 - Development of CRISPR/Cas9-based genome editing for the generation of allogeneic CAR-T cells
• Grantee: Sarah Caroline Gomes de Lima
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/18702-8 - Generation and evaluation of antitumor efficiency of CAR-T cells harboring a T helper 17 phenotype
• Grantee: Heloisa Brand
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/18672-1 - Evaluation of in vivo persistence of T lymphocytes expressing anti-CD19 chimeric antigen receptors
• Grantee: Laís de Castro Batista
• Support Opportunities: Scholarships in Brazil - Scientific Initiation