Delivery Techniques for Enhancing CAR T Cell Therapy against Solid Tumors

Fu, Ruxing; Li, Hongjun; Li, Ruoxin; McGrath, Kyle; Dotti, Gianpietro; Gu, Zhen

doi:10.1002/adfm.202009489

Cited by 39 publications

(22 citation statements)

References 109 publications

(127 reference statements)

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“…[14,15] Despite circumventing intratumoral IB, the dominantly-used local delivery of CAR-T cells by using hydrogel as a reservoir is incapable of adequately activating systematic immune responses, [20] thereby leading to failure in treating multiple nodules and metastasized ones. [21][22][23] Additionally, genetically engineering T cells with new CARs remains ineffective for addressing different concerns (i.e., insuffi-cient CAR-T in vivo) since the re-injected CAR-T cells fail to continually expand, thus highlighting the non-persistence of CAR-T immunotherapy for solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Intraparticle Double‐Scattering‐Decoded Sonogenetics for Augmenting Immune Checkpoint Blockade and CAR‐T Therapy

Wang

Zhang

et al. 2022

Advanced Science

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Genetically arming new chimeric antigen receptors (CARs) on T cells is a prevalent method tofulfill CAR-T immunotherapy. However, this approach fails to completely address the poor infiltration, complex immunosuppressive tumor microenvironment (ITM), and insufficient immune cells, which are recognized as the three dominant hurdles to discouraging the trafficking and persistence of CAR-T and immune checkpoint blockade (ICB) immunotherapies against solid tumors. To address the three hurdles, a sonoimmunity-engineered nanoplatform is designed in which a rattle-type-structured carrier enables intraparticle-double-scattering to generate massive reactive oxygen species (ROS) during the sonodynamic process. Abundant ROS accumulation can directly kill tumor cells, release antigens, and activate systematic immune responses for expanding effector T or CAR-T cells, while alleviating ITM via immunosuppressive macrophage polarization and reduction in pro-tumorigenic cytokine secretion. Furthermore, the co-loaded phosphodiesterase-5 inhibitors release nitric oxide (NO) to impel vascular normalization and open the infiltration barrier (IB) for allowing more T cells to enter into the tumor. Systematic experiments demonstrate the feasibility of such intraparticle-double-scattering-decoded sonogenetics in the sonoimmunity-engineered nanoplatforms for expanding effector T or CAR-T cells, thereby promoting their infiltration into tumors and alleviating ITM. These compelling actions lead to excellent CAR-T and ICB immunotherapies against solid tumors with repressed tumor metastasis.

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Section: Introductionmentioning

confidence: 99%

Intraparticle Double‐Scattering‐Decoded Sonogenetics for Augmenting Immune Checkpoint Blockade and CAR‐T Therapy

Wang

Zhang

et al. 2022

Advanced Science

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“…The remote manipulation of ligand coupling shown in this study has not been reported in previous studies that modulated only linearly shaped ligands in diverse nano-sequences [48] or nano-patterns, [49] and dynamically modulated only the activation of planarly distributed ligands via UV light, [34] or only the stretching of linearly shaped nano-coiled ligands via a magnetic field. [55] Our materials presenting movably couplable ligands offer the tunability of dimensions, [66][67][68][69] alignment, and bioactive ligands of the MLNs and the dimensions of the AuNPs, [70] which can provide fundamental insight to elucidate the dynamic interplay between ligand coupling and integrin recruitment that modulates stem cell adhesion, mechanosensing, and differentiation.…”

Section: Dynamic Ligand Coupling Regulates Focal Adhesion Mechanosens...mentioning

confidence: 99%

Ligand Coupling and Decoupling Modulates Stem Cell Fate

Thangam

Kim

Kang

et al. 2023

Adv Funct Materials

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In natural microenvironment, various proteins containing adhesive ligands in fibrous and non‐fibrous structures dynamically couple and decouple to regulate stem cell fate. Herein, materials presenting movably couplable ligands are developed by grafting liganded gold nanoparticles (AuNPs) to a substrate followed by flexibly grafting liganded movable linear nanomaterials (MLNs) to the substrate via a long bendable linker, thereby creating a space between the MLNs and the AuNPs in the decoupled state. Magnetic control of the MLNs decreases this space via the bending of the linker to couple the MLNs to the AuNPs. Remote control of ligand coupling stimulates integrin recruitment to the coupled ligands, thereby non‐toxically facilitating the focal adhesion, mechanosensing, and potential differentiation of stem cells, which is suppressed by ligand decoupling. Versatile tuning of size, aspect ratio, distributions, and ligands of the MLNs can help to decipher dynamic ligand‐coupling‐dependent stem cell fate to advance regenerative therapies.

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“…The reasons for the slow advancement in CAR-T cells for the treatment of HNSCC are associated with the barriers formed by the unique tumor microenvironment (TME) of solid tumors, and are as follows: (1) physical barriers, including compact tumor structures, tumor stromal cells, etc., (2) physiochemical barriers, including the downregulation of cytokines and acidic, hypoxia and low-nutrient environments and (3) pathological barriers, including immunosuppressive mechanisms, immune checkpoints, tumor antigen loss and heterogeneity, etc. These barriers restrict the infiltration of CAR-T cells into HNSCC, influence the specificity of HNSCC cell targeting and decrease the proliferation and anti-tumor effect of CAR-T cells [ 62 , 63 , 64 ]. Strategies to overcome these three barriers in solid tumors are regarded as the key point of accelerating the clinical translation of CAR-T cell therapy.…”

Section: Barriers Of Car-t Cell Therapy In Hnscc and Potential Solutionsmentioning

confidence: 99%

Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma

Wang

Man

et al. 2023

JCM

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Surgery with the assistance of conventional radiotherapy, chemotherapy and immunotherapy is the basis for head and neck squamous cell carcinoma (HNSCC) treatment. However, with these treatment modalities, the recurrence and metastasis of tumors remain at a high level. Increasingly, the evidence indicates an excellent anti-tumor effect of chimeric antigen receptor T (CAR-T) cells in hematological malignancy treatment, and this novel immunotherapy has attracted researchers’ attention in HNSCC treatment. Although several clinical trials have been conducted, the weak anti-tumor effect and the side effects of CAR-T cell therapy against HNSCC are barriers to clinical translation. The limited choices of targeting proteins, the barriers of CAR-T cell infiltration into targeted tumors and short survival time in vivo should be solved. In this review, we introduce barriers of CAR-T cell therapy in HNSCC. The limitations and current promising strategies to overcome barriers in solid tumors, as well as the applications for HNSCC treatment, are covered. The perspectives of CAR-T cell therapy in future HNSCC treatment are also discussed.

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Delivery Techniques for Enhancing CAR T Cell Therapy against Solid Tumors

Cited by 39 publications

References 109 publications

Intraparticle Double‐Scattering‐Decoded Sonogenetics for Augmenting Immune Checkpoint Blockade and CAR‐T Therapy

Intraparticle Double‐Scattering‐Decoded Sonogenetics for Augmenting Immune Checkpoint Blockade and CAR‐T Therapy

Ligand Coupling and Decoupling Modulates Stem Cell Fate

Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma

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