Systemic administration of polymersomal oncolytic peptide LTX-315 combining with CpG adjuvant and anti-PD-1 antibody boosts immunotherapy of melanoma

Xia, Yifeng; Wei, Jingjing; Zhao, Songsong; Guo, Beibei; Meng, Fenghua; Klumperman, Bert; Zhong, Zhiyuan

doi:10.1016/j.jconrel.2021.06.032

Cited by 32 publications

(26 citation statements)

References 55 publications

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“…CPs could efficiently load ADU-S100 to afford a CDN loading content of 17.2 wt% ( Table S1 ). The loading efficiency for CDN was 86.0%, which was similar to CPs for siRNA and CpG ODN [ 37 , 44 , 45 ] and much higher than other nanoparticles and liposomes for CDNs (<45%) [ 31 , 34 , 46 ]. Notably, CDN-loaded CPs (CPs-CDN) revealed excellent colloidal stability in buffer containing 10% FBS or upon storage for 3 weeks ( Fig.…”

Section: Resultsmentioning

confidence: 71%

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Polymersome-mediated cytosolic delivery of cyclic dinucleotide STING agonist enhances tumor immunotherapy

Zheng

Guo

Qiu

et al. 2022

Bioactive Materials

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Section: Resultsmentioning

confidence: 71%

“…Besides local i.t. injection, polymersomal CDN might also be delivered systemically as reported for CpG and siRNA [ 37 , 44 , 45 ]. The dense PEGylation, neutral surface charge and favorable size of CPs-CDN facilitate effective bypass of phagocytosis [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Polymersome-mediated cytosolic delivery of cyclic dinucleotide STING agonist enhances tumor immunotherapy

Zheng

Guo

Qiu

et al. 2022

Bioactive Materials

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“…Using a multivalent polymer conjugated with an oncolytic peptide also could enhance the membrane lytic property and impose ICD in 4T1 tumor-bearing mice 30 . In addition, the CpG adjuvant and oncolytic peptides LTX-315 co-loaded core-shell nanoparticles exhibited strong immune response, but the synthesis steps were relatively cumbersome and needed the additional anti-PD-L1 antibody to achieve long-term immune memory protection 45 .…”

Section: Discussionmentioning

confidence: 99%

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer

Lu¹,

Zhang²,

Zhou³

et al. 2022

Theranostics

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Rationale: Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically. Methods: Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties. Results: We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both in vitro and in vivo , which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens. Conclusion: Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).

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“…Ran et al reported the magnetic nanoparticles loaded CpG which could exert photothermal therapy (PTT) and greatly activate DC maturation to heat up the TME of TNBC [ 23 ]. We recently developed a polymersomal CpG (NanoCpG) that greatly boosted the anti-cancer immune responses over free CpG in melanoma and in “cold” orthotopic glioma models [ 24 , 25 ]. It should further be noted that NanoCpG facilitates systemic injection and reduces potential immunogenic toxicity of CpG.…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative “cold” triple-negative breast cancer

Guo

Zhao

et al. 2023

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Systemic administration of polymersomal oncolytic peptide LTX-315 combining with CpG adjuvant and anti-PD-1 antibody boosts immunotherapy of melanoma

Cited by 32 publications

References 55 publications

Polymersome-mediated cytosolic delivery of cyclic dinucleotide STING agonist enhances tumor immunotherapy

Polymersome-mediated cytosolic delivery of cyclic dinucleotide STING agonist enhances tumor immunotherapy

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer

Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative “cold” triple-negative breast cancer

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