Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen

Xie, Xiaoling; Hu, Ya-Han; Ye, Tong; Chen, Yiran; Zhou, Lijuan; Li, Feng; Xi, Xiaobo; Wang, Shuang; He, Yanjie; Gao, Xiaoyong; Wei, Wei; Ma, Guanghui; Li, Yuhua

doi:10.1038/s41551-020-00624-6

Cited by 68 publications

(36 citation statements)

References 64 publications

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“…This approach revealed a sustained release over 5 weeks as well as upregulation of chemokines and increased number of antigen-presenting cells at the vaccination site. 32 Our study investigated pharmacokinetics and biodistribution in an in vivo setting, which is one of the main strengths of this study. Combining quantitative measurements with two independent visualization techniques strengthen the study as well.…”

Section: Discussionmentioning

confidence: 99%

Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns

et al. 2021

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Background and Objectives: Current cancer immunotherapeutic treatment with PD-1 inhibitors is administered systemically. However, a local treatment strategy may be advantageous as it could provide targeted drug delivery as well as attenuate side effects seen with systemic treatments. For keratinocyte cancers, where surgical excision is not always applicable, an alternate local treatment approach would be beneficial. This study aims to examine cutaneous pharmacokinetics and biodistribution of the PD-1 inhibitor nivolumab, locally delivered either by ablative fractional laser (AFL)-assisted passive diffusion or active intradermal injection, in vivo. Materials and Methods: In vivo pig skin was either exposed to CO 2 AFL (80 mJ/ mb by two stacked pulses of 40 mJ/mb) at 5% or 15% density followed by topical application of nivolumab (1 mg/ml, 100 µl/10 × 10 mm) or intradermally injected with nivolumab (1 mg/ml, 100 µl). Cutaneous nivolumab delivery was evaluated at different timepoints (0, 1, 2, 4 hours and 2 days) at two tissue depths (100-800 and 900-1600 µm) by ELISA. Visualization of cutaneous biodistribution was shown in vertical tissue sections using HiLyte Fluor TM 488 SE labeled nivolumab for fluorescence microscopy whereas nivolumab was DOTA-tagged with Dysprosium before the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS). Results: Our in vivo study revealed different pharmacokinetic and biodistribution patterns for the AFL-and injection techniques. A superficial horizontal band-like uptake of nivolumab was provided with AFL-assisted passive diffusion whereas a deep focal deposition was seen with active intradermal injection, compared with controls showing remnant deposition on the skin surface. AFL-assisted nivolumab uptake in upper dermis peaked after 4 hours (p < 0.01). The cutaneous concentration of nivolumab achieved by intradermal injection was markedly higher than with AFL, the highest deposition with intradermal injection was detected at time 0 hours in both upper and deep dermis (p < 0.01) and decreased throughout the study period, although the concentration remained higher compared with saline control injections at all time points (0 hours -2 d) (p < 0.01). Conclusion:Local cutaneous delivery of nivolumab with either AFL or intradermal injection revealed two different pharmacokinetic and biodistribution patterns. Passive AFL-assisted diffusion of nivolumab resulted in enhanced uptake after 4 hours, while intradermal actively injected nivolumab showed immediate enhanced cutaneous deposition with retention up to 2 days after

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Section: Discussionmentioning

confidence: 99%

Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns

et al. 2021

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“…Owing to their chemical versatility involving covalent or noncovalent binding, synthetic polymer-based vehicles are a potential tool for vaccine delivery. The most extensively used synthetic biodegradable polymers include poly(lactic-co-glycolic acid) (PLGA), polycaprolactone, polylactic acid, polyglycolic acid, polyvinyl alcohol, polyhydroxybutyric acid, polyethyleneimine, and acrylic polymers [104][105][106][107][108] . An example of an U.S. FDA approved polymer is PLGA, which has excellent biocompatibility and biodegradability, sustained and controlled release of antigens, and the ability to be modified to provide specific functions like lysosomal escape 109 .…”

Section: Polymer-based Vehiclesmentioning

confidence: 99%

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

Liang

Zhao

2021

Cancer Biol. Med.

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Nanomaterial-based delivery vehicles such as lipid-based, polymer-based, inorganics-based, and bio-inspired vehicles often carry distinct and attractive advantages in the development of therapeutic cancer vaccines. Based on various delivery vehicles, specifically designed nanomaterials-based vaccines are highly advantageous in boosting therapeutic and prophylactic antitumor immunities. Specifically, therapeutic vaccines featuring unique properties have made major contributions to the enhancement of antigen immunogenicity, encapsulation efficiency, biocompatibility, and stability, as well as promoting antigen cross-presentation and specific CD8 + T cell responses. However, for clinical applications, tumor-associated antigen-derived vaccines could be an obstacle, involving immune tolerance and deficiency of tumor specificities, in achieving maximum therapeutic indices. However, when using bioinformatics predictions with emerging innovations of in silico tools, neoantigen-based therapeutic vaccines might become potent personalized vaccines for tumor treatments. In this review, we summarize the development of preclinical therapeutic cancer vaccines and the advancements of nanomaterial-based delivery vehicles for cancer immunotherapies, which provide the basis for a personalized vaccine delivery platform. Moreover, we review the existing challenges and future perspectives of nanomaterial-based personalized vaccines for novel tumor immunotherapies.

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“…With the synergism of epitope peptide, PD-1 antibody, and the unique self-healing feature of the microcapsule, a single dose of the vaccine led to the recruitment of activated APCs and significantly improved the infiltration of tumor-specific CTLs. The results indicated that such new vaccine platform could serve as a promising immunotherapy modality for anti-tumor treatment ( 78 ).…”

Section: Improve the Design Of Current Tumor Vaccinesmentioning

confidence: 99%

Enhancing the Efficacy of Tumor Vaccines Based on Immune Evasion Mechanisms

et al. 2021

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Tumor vaccines aim to expand tumor-specific T cells and reactivate existing tumor-specific T cells that are in a dormant or unresponsive state. As such, there is growing interest in improving the durable anti-tumor activity of tumor vaccines. Failure of vaccine-activated T cells to protect against tumors is thought to be the result of the immune escape mechanisms of tumor cells and the intricate immunosuppressive tumor microenvironment. In this review, we discuss how tumor cells and the tumor microenvironment influence the effects of tumor infiltrating lymphocytes and summarize how to improve the efficacy of tumor vaccines by improving the design of current tumor vaccines and combining tumor vaccines with other therapies, such as metabolic therapy, immune checkpoint blockade immunotherapy and epigenetic therapy.

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Therapeutic vaccination against leukaemia via the sustained release of co-encapsulated anti-PD-1 and a leukaemia-associated antigen

Cited by 68 publications

References 64 publications

Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns

Topical delivery of PD‐1 inhibitors with laser‐assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

Enhancing the Efficacy of Tumor Vaccines Based on Immune Evasion Mechanisms

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