GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision

Wang, Kai; Chen, Yuhui; Ahn, Sarah; Zheng, Min; Landoni, Elisa; Dotti, Gianpietro; Savoldo, Barbara; Han, Zongchao

doi:10.1038/s43018-020-00119-y

Cited by 70 publications

(54 citation statements)

References 26 publications

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“…Moreover, CAR-T cell delivery using hydrogels for tumor immunotherapy has also attracted increasing attentions. 380 , 381 …”

Section: In Vitro and In Vivo Potential Applications Of Hydrogelmentioning

confidence: 99%

“…Moreover, CAR-T cell delivery using hydrogels for tumor immunotherapy has also attracted increasing attentions. 380,381 Smart hydrogels for drug delivery and targeted therapy Hydrogels have prominent advantages for drug delivery, especially for those hydrophobic drugs and macromolecule cargos. For instance, the bioavailability of hydrophobic drug like zinc phthalocyanine (ZnPC) is always quite low due to their poor solubility in physiological condition, and they are disabled to be used alone.…”

Section: In Vitro and In Vivo Potential Applications Of Hydrogelmentioning

confidence: 99%

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Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

342

256

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Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.

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“…Moreover, CAR-T cell delivery using hydrogels for tumor immunotherapy has also attracted increasing attentions. 380 , 381 …”

Section: In Vitro and In Vivo Potential Applications Of Hydrogelmentioning

confidence: 99%

Section: In Vitro and In Vivo Potential Applications Of Hydrogelmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

342

256

View full text Add to dashboard Cite

show abstract

“…Unfortunately, the biomaterial scaffolds developed for ACT to date often require complex manufacturing protocols that are not easily tuned to different solid tumor applications ( 10 ). Furthermore, these materials often require invasive surgical implantation procedures to reach tumor sites, hindering translation and limiting the use of these approaches to postresection applications, or have demonstrated applicability in immune-privileged tissues ( 6 , 7 , 9 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors

et al. 2022

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Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.

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“…Immunotherapy has been successfully applied to various types of cancers ( Havel et al, 2019 ). A recent study has proved the efficacy of immunotherapy in eliminating retinoblastoma cells whilst preserving the mouse vision ( Wang et al, 2020 ). However, the treatment of advanced retinoblastoma remains challenging, thus, further therapeutic development is needed ( Abramson et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Immune Cell Infiltration Landscape and Immune-Related Methylation in Retinoblastoma

Mao

Shen

et al. 2022

Front. Genet.

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Retinoblastoma is a common pediatric intraocular cancer, originating from cone precursors. The development of immunotherapies can help eradicate the tumor without vision loss, which would largely improve the quality of life of patients with retinoblastoma. Investigation of the tumor immune microenvironment provides knowledge for developing novel immunotherapies in cancer. However, the immune cell infiltrative landscape of retinoblastoma is unknown. Here, we compared the relative expression of immune gene signatures among 59 patients with retinoblastoma. The patients were divided into two subgroups according to the 28 types of immune cell infiltration (ICI) scores. We found that a subgroup with high ICI scores had increased expression levels of late cone markers, while the other subgroup exhibited larger tumor size and metastasis propensity. Furthermore, hypermethylated genes in the high-ICI subgroup were associated with immune regulation in the tumor microenvironment, suggesting that DNA methylation may play a vital regulatory role in retinoblastoma immunity. Our study provides a comprehensive framework for the systemic analysis of the influences of epigenetic events on the tumor immune microenvironment. We anticipate that our assay can not only provide insights into tumor immune regulation but also open up the perspectives for the identification of novel immunotherapy targets for retinoblastoma.

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GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision

Cited by 70 publications

References 26 publications

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors

Comprehensive Analysis of the Immune Cell Infiltration Landscape and Immune-Related Methylation in Retinoblastoma

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