Combination of genetically engineered T cells and immune checkpoint blockade for the treatment of cancer.
Rafaela RossettiHeloísa BrandSarah Caroline Gomes LimaIzadora Peter FurtadoRoberta Maraninchi SilveiraDaianne Maciely Carvalho FantaciniDimas Tadeu CovasLucas Eduardo Botelho de SouzaPublished in: Immunotherapy advances (2022)
Immune checkpoint (IC) blockade using monoclonal antibodies is currently one of the most successful immunotherapeutic interventions to treat cancer. By reinvigorating antitumor exhausted T cells, this approach can lead to durable clinical responses. However, the majority of patients either do not respond or present a short-lived response to IC blockade, in part due to a scarcity of tumor-specific T cells within the tumor microenvironment. Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CARs) or engineered T-cell receptors (TCRs) provide the necessary tumor-specific immune cell population to target cancer cells. However, this therapy has been considerably ineffective against solid tumors in part due to IC-mediated immunosuppressive effects within the tumor microenvironment. These limitations could be overcome by associating adoptive cell transfer of genetically engineered T cells and IC blockade. In this comprehensive review, we highlight the strategies and outcomes of preclinical and clinical attempts to disrupt IC signaling in adoptive T-cell transfer against cancer. These strategies include combined administration of genetically engineered T cells and IC inhibitors, engineered T cells with intrinsic modifications to disrupt IC signaling, and the design of CARs against IC molecules. The current landscape indicates that the synergy of the fast-paced refinements of gene-editing technologies and synthetic biology and the increased comprehension of IC signaling will certainly translate into a novel and more effective immunotherapeutic approaches to treat patients with cancer.
Keyphrases
- cell therapy
- papillary thyroid
- squamous cell
- end stage renal disease
- stem cells
- squamous cell carcinoma
- chronic kidney disease
- ejection fraction
- physical activity
- single cell
- newly diagnosed
- type diabetes
- skeletal muscle
- peritoneal dialysis
- metabolic syndrome
- adipose tissue
- lymph node metastasis
- bone marrow
- insulin resistance
- combination therapy
- glycemic control
- chemotherapy induced