Advancing cell-based cancer immunotherapy through stem cell engineering

Li, Yan-Ruide; Dunn, Zachary Spencer; Yu, Yanqi; Li, Miao; Wang, Pin; Yang, Lili

doi:10.1016/j.stem.2023.02.009

Cited by 35 publications

(17 citation statements)

References 258 publications

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“…Currently, CARs have been widely armed in immune cells like T cells, NK cells and macrophages (reviewed in refs. 5 , 69 , 70 ). Besides, innate T cells including invariant natural killer T (iNKT) cells, mucosal associated invariant T (MAIT) cells and gamma delta T (γδT) cells have been developed as promising immune effector cells, because they display intrinsic antitumor microenvironment (TME) capacities and minimal risks of graft versus host disease (GvHD) (reviewed in refs.…”

Section: Engineering Of Synthetic Receptorsmentioning

confidence: 99%

“…More importantly, a combination of different synthetic receptor systems can exhibit synergistic effects and further enhance their performance, as studies have shown that synNotch CAR T cells exhibit a significantly enhanced safety and antitumor efficacy by combinatorial antigen recognition 40 , 167 , 168 , 189 , 252 or ultrasensitive antigen-density sensing. 190 As engineered stem cell therapy emerges, synthetic receptors can also be applied to engineer pluripotent stem cell-derived cell products 3 , 70 , 175 (Fig. 7 b, c), potentially being used to enhance their survival and engraftment ability via programmed communications with the host microenvironment 2 , 3 , 253 , 254 (Fig.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

“…After being infused back into patients, these engineered immune cells interact with antigens on the tumor cells, leading to the activation of CAR immune cells to achieve cancer-killing. 70 , 333 b , c Synthetic receptors could be integrated into PSCs to enhance original or program novel functionalities of the differentiated derivates for developing next-generation cellular therapeutics. b PSCs can differentiate into various cell types, like hepatocytes, neurons, muscle cells, etc., which are suitable for transplantation.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

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Programmable synthetic receptors: the next-generation of cell and gene therapies

Teng,

Cui,

Zhou

et al. 2024

Sig Transduct Target Ther

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Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat diseases. However, concerns over the safety and efficacy require to be further addressed in order to realize their full potential. Synthetic receptors, a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules, have been rapidly developed and applied as a powerful solution. Delicately designed and engineered, they can be applied to finetune the therapeutic activities, i.e., to regulate production of dosed, bioactive payloads by sensing and processing user-defined signals or biomarkers. This review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical research. With a special focus on four synthetic receptor systems at the forefront, including chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, we address the generalized strategies to design, construct and improve synthetic receptors. Meanwhile, we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

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Section: Engineering Of Synthetic Receptorsmentioning

confidence: 99%

Section: Conclusion and Perspectivementioning

confidence: 99%

Section: Conclusion and Perspectivementioning

confidence: 99%

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Programmable synthetic receptors: the next-generation of cell and gene therapies

Teng,

Cui,

Zhou

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

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“…While these cells offer great potential for advancing cancer research, their use necessitates ethical considerations. Researchers must ensure that individuals providing cells for iPSC research are adequately informed about the purpose, risks, and potential benefits of the research [ 38 , 739 ]. Respect for donor autonomy and privacy should be maintained throughout the process, including secure data management and confidentiality.…”

Section: Ethical and Legal Considerationsmentioning

confidence: 99%

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

Chehelgerdi,

Behdarvand Dehkordi,

Chehelgerdi

et al. 2023

Mol Cancer

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The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing, and tailored medical interventions. This review article will provide an overview of the science behind iPSCs, the current limitations and challenges in iPSC-based cancer therapy, the ethical and social implications, and the comparative analysis with other stem cell types for cancer treatment. The article will also discuss the applications of iPSCs in tumorigenesis, the future of iPSCs in tumorigenesis research, and highlight successful case studies utilizing iPSCs in tumorigenesis research. The conclusion will summarize the advancements made in iPSC-based tumorigenesis research and the importance of continued investment in iPSC research to unlock the full potential of these cells.

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“…3,4 Despite their significance, efficient delivery of genetic material to stem cells and immune cells remains a challenge, due to low transduction efficiency and compromised cellular fitness after transduction. 5,6 Various strategies are employed to improve successful gene deliveries. 2,7 These include mechanical techniques such as electroporation, chemical approaches involving lipid or nanoparticle carriers, and biologically assisted methods using viral or bacterial vectors.…”

Section: Introductionmentioning

confidence: 99%

Nanotopography boosts cellular uptake by inducing macropinocytosis

Aramesh,

Yu,

Essand

et al. 2023

Preprint

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Efficient cellular uptake of biomolecules, including genetic material, mRNA, proteins, and nanoparticles, requires novel approaches to overcome inherent cellular barriers. This study investigates how nanotopographical cues from nanoporous surfaces impact the uptake efficiency of diverse molecules by cells. The results demonstrate that cellular uptake efficiency increases significantly on nanoporous surfaces compared to flat surfaces. Notably, this process is found to be dependent on the size and morphology of the nanopores, reaching its peak efficacy with blind pores of 400 nm in size. Enhanced genetic transduction on nanoporous surfaces were observed for multiple vectors, including lentiviruses, baculoviruses, and mRNA molecules. The versatile nature of this approach allows co-transfection of cells with multiple mRNA vectors. Moreover, the nanoporous platform was used for efficient and fast manufacturing of CAR-T cells through lentiviral transduction. Furthermore, we pinpoint macropinocytosis as the predominant mechanism driving increased cellular uptake induced by the nanoporous surfaces. The method introduced here for enhancing genetic transduction of cells has applications in immunotherapy research, drug delivery, and cell engineering.

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Advancing cell-based cancer immunotherapy through stem cell engineering

Cited by 35 publications

References 258 publications

Programmable synthetic receptors: the next-generation of cell and gene therapies

Programmable synthetic receptors: the next-generation of cell and gene therapies

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

Nanotopography boosts cellular uptake by inducing macropinocytosis

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