Combining mannose receptor mediated nanovaccines and gene regulated PD-L1 blockade for boosting cancer immunotherapy

Abstract

Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors. However, it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses. Toward this objective, we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity. Here, we fabricate a mannose modified PLL-RT (Man-PLL-RT) mediated nanovaccines with dendritic cells (DCs) targeting capacity. Man-PLL-RT is capable of co-encapsulating with antigen (ovalbumin, OVA) and adjuvant (unmethylated cytosine-phosphate-guanine, CpG) by electrostatic interaction. This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis, maturation and cross presentation in DCs. However, the nanovaccines arouse limited inhibition of tumor growth, which is mainly due to the immunosuppressed microenvironment of tumors. Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice. The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.

Bioengineered nanogels for cancer immunotherapy

“…14c). 247 The obtained NVs could be combined with gene-regulated PD-L1 blockade (NPs), thus alleviating the tumour immune tolerance microenvironment caused by the upregulation of pro-inflammatory cytokines (TNF-α, IFN-γ). Whether as prophylactic vaccines or tumour therapeutic vaccines, the combination of NVs and NPs suppressed the growth of melanoma-bearing mice and significantly increased Tem cells in the spleen, and effectively limited the recurrence and metastasis of the tumour.…”

Nanovaccines for Cancer Prevention and Immunotherapy: An Update Review

“…The combination of immunotherapy with anti-PD-L1 antibody and nanovaccines revealed that anti-tumor immune responses were enhanced in a 4T1 breast cancer model [ 116 ]. In several other recent studies, it was revealed that the collaborative approaches using nano-based cancer vaccines and immune checkpoint blockers could improve the effectiveness of immunotherapy [ 122 , 123 , 124 ].…”

Novel Approaches in the Immunotherapy of Multiple Sclerosis: Cyclization of Myelin Epitope Peptides and Conjugation with Mannan

“…Mannan, a poly-mannose isolated from the cell wall of yeasts, has been shown to exert immunomodulatory effects in the cancer settings in vitro [ 45 , 46 , 47 , 48 , 49 , 50 ], in vivo (inbred mice, transgenic mice, rats, rabbits, and chickens) [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ], in rhesus macaques [ 63 , 64 , 65 ], and in human clinical trials [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Mannan targets antigens to the mannose receptor, antigens endocytosed for MHC class I or II presentation, and modulation of appropriate T cells [ 45 , 53 , 54 , 55 , 76 , 77 , 78 , 79 , 80 , 81 ]. In relation to autoimmune disorders, mannan conjugates (i) represent a new class of immunoregulators that directly and selectively target a population of immune cells that are implicated in the pathogenesis and progression of disease; (ii) provide first line treatment that selectively tolerates or inactivates disease-inducing cells in patients and also prevents progression of disease by stopping diversification of the autoimmune response to additional epitopes; (iii) allows easier formulation of newly discovered molecules within the mannan matrix platform; and (iv) can achieve block-buster status as a global vaccine drug for eff...…”