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Engineering CAR-T cells for solid tumors: bispecific antigen targeting, tumor microenvironment modulation, and toxicity control
Designing CAR-T cells for solid tumors with dual targeting, tumor environment adjustment, and side effect management
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Abstract
CAR-T cell therapy has shown limited efficacy in solid tumors due to challenges like antigen heterogeneity and immunosuppressive environments.
- Advancements in CAR-T therapy focus on enhancing persistence and function through co-stimulatory domains and cytokine-armed approaches.
- Comparison of viral and non-viral delivery systems reveals that CRISPR allows for improved specificity via multiplex edits.
- Innovations like dual-targeting CARs and hypoxia-inducible CARs may improve targeting to tumor sites by addressing antigen variability.
- Engineering chemokine receptors can enhance T cell infiltration into tumors, while armored CARs can modify the tumor microenvironment.
- Nanobody-based CAR-T cells are associated with increased stability and reduced immunogenicity compared to traditional constructs.
- Clinical trials of bispecific CAR-Ts show potential, but issues such as manufacturing complexity and off-target effects remain.
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