Getting better mileage with logically primed CARs

Chen, Laurence C.; Hou, Andrew J.; Chen, Yvonne Y.

doi:10.1016/j.medj.2021.06.002

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…T cells engineered with prime-andkill circuits induce CAR-driven cytotoxicity that is spatially limited only to the proximity of priming cells, preventing offtumor killing in distant normal tissues that carry the killing antigen but lack the priming antigen. 231,430,431 CAR-NK In addition to T cells, NK cells can also be engineered to express CARs. NK cells have the same capabilities as CD8 + cytotoxic T cells but they are not dependent on MHC-I -mediated tumor neoantigen presentation.…”

Section: Genetically Engineered Anti-tumor Immune Cells Immune Cells ...mentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

244

150

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Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

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Section: Genetically Engineered Anti-tumor Immune Cells Immune Cells ...mentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

244

150

View full text Add to dashboard Cite

show abstract

“…Instead of being triggered by biophysical methods, the SynNotch CAR system is an artificial dual-receptor genetic circuit that requires a combination of two different antigens (AND-gate) to initiate CAR expression and activate T cell cytotoxicity. The first step of the AND-gate signaling circuit requires activating an engineered syn-Notch receptor recognizing the first antigen A. Antigen A recognition leads to cleavage of synNotch and release of an orthogonal transcription factor that activates the expression of CAR directing T cells toward a second tumor antigen B [110][111][112][113]. The original system was further modified to accommodate the recognition of various tumor antigen combinations such as ROR1/EpCAM or ROR1/B7-H3 in the breast cancer model [114], GD2/ B7-H3 in neuroblastoma [115], EGFRvIII SynNotch that induces expression of EohA2/Il13Ra2 tandem CAR for treatment of glioblastoma [116], or ALPPL2 combined with MCAM or HER2 synNotch CAR combinatorial antigen circuits [117].…”

Section: Synthetic Notch (Synnotch) Logic (And)-gate Car Technologymentioning

confidence: 99%

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

et al. 2023

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Cancer immunotherapies utilizing genetically engineered T cells have emerged as powerful personalized therapeutic agents showing dramatic preclinical and clinical results, particularly in hematological malignancies. Ectopically expressed chimeric antigen receptors (CARs) reprogram immune cells to target and eliminate cancer. However, CAR T cell therapy's success depends on the balance between effective anti-tumor activity and minimizing harmful side effects. To improve CAR T cell therapy outcomes and mitigate associated toxicities, scientists from different fields are cooperating in developing next-generation products using the latest molecular cell biology and synthetic biology tools and technologies. The immunotherapy field is rapidly evolving, with new approaches and strategies being reported at a fast pace. This comprehensive literature review aims to provide an up-to-date overview of the latest developments in controlling CAR T cell activity for improved safety, efficacy, and flexibility.

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Getting better mileage with logically primed CARs

Cited by 2 publications

References 9 publications

Neoantigens: promising targets for cancer therapy

Neoantigens: promising targets for cancer therapy

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility

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