CAR T cells: engineered immune cells to treat brain cancers and beyond

Abstract

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13Rα2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells’ promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.

From glioma gloom to immune bloom: unveiling novel immunotherapeutic paradigms-a review

“…Its interaction with TLT-2 on immune cells, including CD8+ T cells, has contradictory effects, supporting proinflammatory responses or reducing Th1 immune activity. It is expressed in hematological cancers and solid tumors, including high-grade gliomas [ 122 ]. B7-H3 inhibits T-cell activation and proliferation, driving tumor immune evasion via diverse signaling pathways [ 123 ].…”

Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities

“…This cutting-edge immunotherapy, including CAR-T cells, has shed new light upon the future of refractory tumors. Notably, it provides a potential solution for the persistent uncertainties surrounding the positive margins of surgical resection and radiotherapy for intracranial tumors [ 200 ]. Currently, a phase 1 clinical trial (NCT03696030) of HER2-targeted CAR-T cells in the treatment of HER-2-positive breast cancer patients with recurrent brain or leptomeningeal metastases is in progress, and other basic frontier experiments regarding BM have also been carried out (Table 2 ).…”

A DNA octahedral amplifier for endogenous circRNA detection and bioimaging in living cells and its biomarker study

“…Some traditional approaches have been widely used to study circRNAs, including RNA sequencing (RNA-seq), northern blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH). [12][13][14][15] Nevertheless, traditional approaches are only used to study the circRNAs in cell lysates or fixed cells. The result does not reflect the real physiological environment of cells and low abundance circRNA expression levels in living cells.…”