Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Chen, Tao; Xue, Yucheng; Wang, Shengdong; Lu, Junyan; Zhou, Hao; Zhang, Wenkan; Zhou, Zhiyi; Li, Binghao; Li, Yong; Wang, Zenan; Li, Changwei; Yinwang, Eloy; Sun, Hangxiang; Shen, Yihang; Diarra, Mohamed Diaty; Ge, Chunhua; Chai, Xupeng; Mou, Haochen; Peng, Lin; Ye, Zhaoming

doi:10.1016/j.bioactmat.2022.11.022

Cited by 4 publications

(7 citation statements)

References 48 publications

(69 reference statements)

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“…The tumor-specific targeting peptide was screened using phage display biopanning technology in preliminary experiments. [19,20] In this study, peptides with a specific targeting ability for K7M2, named KTP, were conjugated to the cell membrane of macrophages using a non-genetic modification of PA. This approach demonstrated high efficacy in anchoring peptides to macrophage cell membranes.…”

Section: Discussionmentioning

confidence: 99%

“…In our preliminary study, we screened and synthesized a peptide (QYW NIQ NGP YGG) specifically targeting K7M2 osteosarcoma, named K7M2-targeted peptide (KTP) [19,20] After palmitic acid (PA) modification, KTP became PA-KTP with the ability to anchor to cell membranes. In this study, we designed a targeted therapeutic strategy for the treatment of macrophages.…”

Section: Introductionmentioning

confidence: 99%

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ZIF‐8‐Encapsulated Pexidartinib Delivery via Targeted Peptide‐Modified M1 Macrophages Attenuates MDSC‐Mediated Immunosuppression in Osteosarcoma

Dong,

Chai,

Xue

et al. 2024

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Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti‐tumor efficacy of macrophages. K7M2‐target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib‐loaded ZIF‐8 nanoparticles (P@ZIF‐8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF‐8 and are named P@ZIF/M1‐KTP. The tumor volumes in the P@ZIF/M1‐KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1‐KTP exhibited enhanced anti‐tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1‐KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA‐seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1‐KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ZIF‐8‐Encapsulated Pexidartinib Delivery via Targeted Peptide‐Modified M1 Macrophages Attenuates MDSC‐Mediated Immunosuppression in Osteosarcoma

Dong,

Chai,

Xue

et al. 2024

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“…Other strategies have also been used to enhance T cell infiltration. For instance, Tao et al infused tumor-specific targeting peptides identified by phage display biopanning technology onto the T cell membranes to precisely target highly heterogeneous solid tumors while also significantly increasing CD8 + T cell infiltration [ 175 ]. Interestingly, scientists found that glucose/mannose analogue 2-deoxy-D-glucose, a medication that prevented N-glycan synthesis, eliminated the protective effect of N-glycans on tumors and made solid tumors more accessible for CAR T cells to infiltrate and eradicate [ 176 ].…”

Section: Challenges and Strategies Of Act In Solid Tumorsmentioning

confidence: 99%

The potential and promise for clinical application of adoptive T cell therapy in cancer

Li,

Zheng,

Liu

et al. 2024

J Transl Med

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Adoptive cell therapy has revolutionized cancer treatment, especially for hematologic malignancies. T cells are the most extensively utilized cells in adoptive cell therapy. Currently, tumor-infiltrating lymphocytes, T cell receptor-transgenic T cells and chimeric antigen receptor T cells are the three main adoptive T cell therapies. Tumor-infiltrating lymphocytes kill tumors by reinfusing enlarged lymphocytes that naturally target tumor-specific antigens into the patient. T cell receptor-transgenic T cells have the ability to specifically destroy tumor cells via the precise recognition of exogenous T cell receptors with major histocompatibility complex. Chimeric antigen receptor T cells transfer genes with specific antigen recognition structural domains and T cell activation signals into T cells, allowing T cells to attack tumors without the assistance of major histocompatibility complex. Many barriers have been demonstrated to affect the clinical efficacy of adoptive T cell therapy, such as tumor heterogeneity and antigen loss, hard trafficking and infiltration, immunosuppressive tumor microenvironment and T cell exhaustion. Several strategies to improve the efficacy of adoptive T cell therapy have been explored, including multispecific chimeric antigen receptor T cell therapy, combination with immune checkpoint blockade, targeting the immunosuppressive tumor microenvironment, etc. In this review, we will summarize the current status and clinical application, followed by major bottlenecks in adoptive T cell therapy. In addition, we will discuss the promising strategies to improve adoptive T cell therapy. Adoptive T cell therapy will result in even more incredible advancements in solid tumors if the aforementioned problems can be handled. Graphical abstract

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“…The cell membrane skeleton is a phospholipid bilayer structure allowing the spontaneous insertion of synthetic materials with hydrophobic anchors or "tails" driven by the hydrophobic effect. [71][72][73] The commonly used hydrophobic anchors include lipids (phospholipids 21,26,[73][74][75][76][77][78][79][80] and cholesterols [81][82][83][84][85][86][87][88][89][90][91][92] ), alkane chains [93][94][95][96][97][98] and oleyl chains. [99][100][101][102][103][104][105] They can be categorized into single and multiple anchors based on the number of hydrophobic anchors.…”

Section: Hydrophobic Insertionmentioning

confidence: 99%

Advancing cell surface modification in mammalian cells with synthetic molecules

Yang,

Yao,

Wang

et al. 2023

Chem. Sci.

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Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Cited by 4 publications

References 48 publications

ZIF‐8‐Encapsulated Pexidartinib Delivery via Targeted Peptide‐Modified M1 Macrophages Attenuates MDSC‐Mediated Immunosuppression in Osteosarcoma

ZIF‐8‐Encapsulated Pexidartinib Delivery via Targeted Peptide‐Modified M1 Macrophages Attenuates MDSC‐Mediated Immunosuppression in Osteosarcoma

The potential and promise for clinical application of adoptive T cell therapy in cancer

Advancing cell surface modification in mammalian cells with synthetic molecules

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