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Updated: May 12, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
In situ induction of multivalent PD-L1 antibody secretion to enhance cancer immunotherapy
Li-Li Chen1, Shi-Kun Zhou1, Shui-Qing Jiang1
1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, P. R. China. yaliu@scut.edu.cn.
Immune checkpoint blockade (ICB) therapy has transformed cancer treatment; however, its therapeutic efficacy remains limited, largely due to insufficient intratumoral accumulation of checkpoint-blocking antibodies (e.g., anti-PD-L1) and suboptimal immune activation. To overcome these limitations, we design a multivalent PD-L1 antibody (MV-αPD-L1) that structurally mimics the hexameric architecture of IgM and encapsulates its encoding plasmid into a lipid-assisted polymer nanoparticle. The resulting gene nanomedicine, NPMV-αPD-L1, enables in situ secretion of MV-αPD-L1 within the tumor microenvironment, achieving high intratumoral antibody concentrations and enhanced PD-L1 binding avidity. Following intravenous administration, NPMV-αPD-L1 effectively blocks PD-L1, promotes CD8+ T-cell infiltration, and enhances cytotoxic T-cell activation, leading to robust tumor inhibition. To further improve tumor specificity, a melanoma-specific tyrosinase (Tyr) promoter is incorporated to generate NPTyr-MV-αPD-L1, which enables selective intratumoral secretion of MV-αPD-L1 in melanoma. This tumor-restricted antibody production induces potent, localized T-cell activation while minimizing off-target effects, thereby achieving superior therapeutic efficacy with an improved safety profile. Collectively, this strategy reprograms the tumor into a self-sustaining "antibody factory", providing a versatile and safe platform to amplify ICB efficacy through durable and tumor-specific immune modulation.
Immune checkpoint blockade (ICB) therapy has transformed cancer treatment; however, its therapeutic efficacy remains limited, largely due to insufficient intratumoral accumulation of checkpoint-blocking antibodies (e.g., anti-PD-L1) and suboptimal immune activation. To overcome these limitations, we design a multivalent PD-L1 antibody (MV-αPD-L1) that structurally mimics the hexameric architecture of IgM and encapsulates its encoding plasmid into a lipid-assisted polymer nanoparticle. The resulting gene nanomedicine, NPMV-αPD-L1, enables in situ secretion of MV-αPD-L1 within the tumor microenvironment, achieving high intratumoral antibody concentrations and enhanced PD-L1 binding avidity. Following intravenous administration, NPMV-αPD-L1 effectively blocks PD-L1, promotes CD8+ T-cell infiltration, and enhances cytotoxic T-cell activation, leading to robust tumor inhibition. To further improve tumor specificity, a melanoma-specific tyrosinase (Tyr) promoter is incorporated to generate NPTyr-MV-αPD-L1, which enables selective intratumoral secretion of MV-αPD-L1 in melanoma. This tumor-restricted antibody production induces potent, localized T-cell activation while minimizing off-target effects, thereby achieving superior therapeutic efficacy with an improved safety profile. Collectively, this strategy reprograms the tumor into a self-sustaining "antibody factory", providing a versatile and safe platform to amplify ICB efficacy through durable and tumor-specific immune modulation.
