Gene-modified T cell therapy for cancer: Current challenges and potential solutions

Abstract

Immunotherapy has achieved significant breakthroughs in patients with hematological diseases and various cancers. The adoptive transfer of T cells, especially gene-modified T cells such as chimeric antigen receptor T (CAR-T) cells and T cell receptor-engineered T (TCR-T) cells, is developing rapidly. Since 2017, eight CAR-T cell products have been approved for the treatment of hematological diseases, such as refractory or relapsed acute B lymphoblastic leukemia, specific subtypes of B cell lymphoma, and multiple myeloma. The first TCR-T cell product, Kimmtrak, was approved for the treatment of unresectable or metastatic uveal melanoma in March 2022. However, there are still many problems, including side effects, relapse, high demand for individualization, and expensive cost in hematological diseases, tumor heterogeneity, antigen escape, poor immune cell infiltration ability, immunosuppressive microenvironment, and low response in solid tumors. With the in-depth exploration of tumor immunology and the development of genetic engineering technology, many novel strategies for improving the anti-tumor effect and safety of gene-modified T cell immunotherapy have been attempted. This paper presents a systematic review of the literature on CAR-T cell and TCR-T cell therapy, focusing on applications, clinical trials, problems, and potential solutions.

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

“…Wang et al found through immunohistochemical analysis of TLR4 after SAH that TLR4 in neurons after SAH is significantly up-regulated [ 18 ]. Islam et al concluded through the analysis of TLR4-specific gene knockout in microglia, astrocytes and neurons in the SAH mouse model that TLR4 is expressed in microglia, and the activation of TLR4 in microglia after SAH can cause nerve injury [ 130 , 131 ]. Thus far, TLR4 up-regulation in neurons and microglia after SAH has been proven.…”

Nanoquantification of RUNX2 by a 1,1′-carbonyldiimidazole-diamond mediated sandwich assay for osteogenic differentiation

“…Various biomarkers play a crucial role in diverse medical applications, including diagnosis, drug delivery, and therapeutics [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] ]. Biosensors, utilizing biological molecules or organisms, are employed to detect the presence of specific substances in biological fluids, facilitating the identification of biomarkers for disease diagnosis [ 21 , 22 ].…”