Interval- and cycle-dependent combined effect of STING agonist loaded lipid nanoparticles and a PD-1 antibody

Khalifa, Alaa M.; Nakamura, Takashi; Sato, Yusuke; Sato, Takanori; Hyodo, Mamoru; Hayakawa, Yoshihiro; Harashima, Hideyoshi

doi:10.1016/j.ijpharm.2022.122034

Cited by 11 publications

(12 citation statements)

References 57 publications

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“…Furthermore, a simultaneous combination treatment of anti‐PD‐1 and anti‐CTLA‐4 with STING‐agonist‐containing liposomes effectively reduced the number of pulmonary metastatic nodules in a mouse melanoma lung metastasis model, whereas free cGAMP + anti‐PD‐1 + anti‐CTLA‐4 did not 420 . Related to this, the delivery protocol needs to be carefully designed, setting parameters of interval time and treatment cycle for STING‐LNP and ICI therapy in order to achieve the best antitumor effects 423 . Additional studies will be needed to analyze whether the liposomal formulation as a delivery platform for combinational STING therapies can be expanded to other therapeutic approaches that are aimed at amplifying T‐cell function, such as agonistic mAbs against various receptors (e.g., 4‐1BB (CD137), OX40 (CD134), CD28, CD27, etc.…”

Section: Liposomally Supported Sting Agonists In Combination With Oth...mentioning

confidence: 99%

Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

Yang

Zhou

et al. 2023

MedComm

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Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation‐related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type‐specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno‐oncology therapy with a focus on lipid‐based NPs (lipid‐NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid‐NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid‐NPs to enhance cancer immunotherapy.

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Section: Liposomally Supported Sting Agonists In Combination With Oth...mentioning

confidence: 99%

Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

Yang

Zhou

et al. 2023

MedComm

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“…This conclusion is consistent with the claim that the antitumor activity of tumor immunotherapy can be assessed by the immune status in the TME ( 40 ). Furthermore, their research group also paid close attention to the importance of the treatment protocol setting of the combined application of SING-LNP and PD-1 antibody, such as the number of cycles of administration, and the order and interval between therapy administration ( 41 ).…”

Section: Nanomedicine Targeting Activation Of Sting In the Cancer Imm...mentioning

confidence: 99%

Nanomedicines targeting activation of STING to reshape tumor immune microenvironment and enhance immunotherapeutic efficacy

et al. 2023

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Immunotherapy has greatly enhanced the effectiveness of cancer treatments, but the efficacy of many current immunotherapies is still limited by the tumor-suppressive immune microenvironment. Multiple studies have shown that activating the stimulation of IFN genes (STING) pathway and inducing innate immunity can significantly impact the tumor immune microenvironment and improve antitumor therapy. While natural or synthetic STING agonists have been identified or developed for preclinical and clinical use, small molecule agonists have limited utility due to degradation and lack of targeting. As such, the delivery and release of STING agonists into tumor tissue is a major challenge that must be addressed in order to further advance the use of STING agonists. To address this challenge, various nanomedicines have been developed. In this paper, we concisely review the antitumor immunotherapeutic mechanisms of STING agonists, highlighting the latest developments in STING agonists and the current progress of nanomedicines for activating STING. We classify the different nanomedicines according to the STING agonists they utilize in order to facilitate understanding of recent advances in this field. Finally, we also discuss the prospects and challenges of this field.

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“…Similarly, crystalline ursolic acid in a liposomal formulation also demonstrated remodeling of the immunosuppressive environment but had limited antitumor efficacy in a 4T1 breast cancer mouse model. 144 Many immunotherapy approaches use a STING agonist, such as liposomal CpG for use in colon cancer and melanoma, 154,162 liposomal cyclic diguanylate (di-GMP) in melanoma, 161,167,187 and liposomal cGAMP for breast cancer. 141 Dane et al developed a novel approach of using lipid nanodiscs to carry cyclic dinucleotides (Figure 7d).…”

Section: Immunotherapymentioning

confidence: 99%

“…Many immunotherapy approaches use a STING agonist, such as liposomal CpG for use in colon cancer and melanoma, 154,162 liposomal cyclic diguanylate (di‐GMP) in melanoma, 161,167,187 and liposomal cGAMP for breast cancer 141 . Dane et al developed a novel approach of using lipid nanodiscs to carry cyclic dinucleotides (Figure 7d).…”

Section: Intravenous Delivery Of Lipid Nanoparticlesmentioning

confidence: 99%

A landscape of recent advances in lipid nanoparticles and their translational potential for the treatment of solid tumors

Paun,

Jurchuk,

Tabrizian

2023

Bioengineering & Transla Med

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Lipid nanoparticles (LNPs) are biocompatible drug delivery systems that have found numerous applications in medicine. Their versatile nature enables the encapsulation and targeting of various types of medically relevant molecular cargo, including oligonucleotides, proteins, and small molecules for the treatment of diseases, such as cancer. Cancers that form solid tumors are particularly relevant for LNP‐based therapeutics due to the enhanced permeation and retention effect that allows nanoparticles to accumulate within the tumor tissue. Additionally, LNPs can be formulated for both locoregional and systemic delivery depending on the tumor type and stage. To date, LNPs have been used extensively in the clinic to reduce systemic toxicity and improve outcomes in cancer patients by encapsulating chemotherapeutic drugs. Next‐generation lipid nanoparticles are currently being developed to expand their use in gene therapy and immunotherapy, as well as to enable the co‐encapsulation of multiple drugs in a single system. Other developments include the design of targeted LNPs to specific cells and tissues, and triggerable release systems to control cargo delivery at the tumor site. This review paper highlights recent developments in LNP drug delivery formulations and focuses on the treatment of solid tumors, while also discussing some of their current translational limitations and potential opportunities in the field.

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Interval- and cycle-dependent combined effect of STING agonist loaded lipid nanoparticles and a PD-1 antibody

Cited by 11 publications

References 57 publications

Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy

Nanomedicines targeting activation of STING to reshape tumor immune microenvironment and enhance immunotherapeutic efficacy

A landscape of recent advances in lipid nanoparticles and their translational potential for the treatment of solid tumors

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