SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

N’Guessan, Kombo F.; Patel, Priyankaben H.; Qi, Xiaoyang

doi:10.1186/s12964-019-0476-6

Cited by 24 publications

(29 citation statements)

References 44 publications

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“…However, these cells are sensitive to SapC-DOPS treatment, suggesting that SapC-DOPS can be used as a combination therapy for cancer cells with high PS exposure during radiation therapy 163 . A recent review focusing on cancer therapy treatments with SapC-DOPS is available 164 .…”

Section: Ps Binding Molecules and Cancer Therapymentioning

confidence: 99%

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Chang

Xiao

et al. 2020

Theranostics

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Cancer is a leading cause of mortality and morbidity worldwide. Despite major improvements in current therapeutic methods, ideal therapeutic strategies for improved tumor elimination are still lacking. Recently, immunotherapy has attracted much attention, and many immune-active agents have been approved for clinical use alone or in combination with other cancer drugs. However, some patients have a poor response to these agents. New agents and strategies are needed to overcome such deficiencies. Phosphatidylserine (PS) is an essential component of bilayer cell membranes and is normally present in the inner leaflet. In the physiological state, PS exposure on the external leaflet not only acts as an engulfment signal for phagocytosis in apoptotic cells but also participates in blood coagulation, myoblast fusion and immune regulation in nonapoptotic cells. In the tumor microenvironment, PS exposure is significantly increased on the surface of tumor cells or tumor cell-derived microvesicles, which have innate immunosuppressive properties and facilitate tumor growth and metastasis. To date, agents targeting PS have been developed, some of which are under investigation in clinical trials as combination drugs for various cancers. However, controversial results are emerging in laboratory research as well as in clinical trials, and the efficiency of PS-targeting agents remains uncertain. In this review, we summarize recent progress in our understanding of the physiological and pathological roles of PS, with a focus on immune suppressive features. In addition, we discuss current drug developments that are based on PS-targeting strategies in both experimental and clinical studies. We hope to provide a future research direction for the development of new agents for cancer therapy.

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Section: Ps Binding Molecules and Cancer Therapymentioning

confidence: 99%

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Chang

Xiao

et al. 2020

Theranostics

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“…Finally, in the third theme, contributed by Burstyn-Cohen et al [5], Dayoub et al [6], and N'Guessan et al [7], these authors converge on a unifying emerging theme that describes current ideas that PS externalization is a potential targeting strategy in cancer biology. In the review by Burstyn-Cohen and Maimon, the authors first describe the interplay between externalized PS on apoptotic and stressed cells in the context of Tyro3, Axl, and Mertk (TAM) receptor activation, a series of homologous receptors that bridge PS via their ligands Protein S (Pros1) and Growth-arrest specific 6 (Gas6).…”

Section: Introductionmentioning

confidence: 97%

Biology of phosphatidylserine (PS): basic physiology and implications in immunology, infectious disease, and cancer

Calianese

Birge

2020

Cell Commun Signal

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Phosphatidylserine (PS) is an anionic phospholipid found on the membranes of a variety of organelles throughout the cell, most notably the plasma membrane. Under homeostatic conditions, PS is typically restricted to the inner leaflet of the plasma membrane. However, during cellular activation and/or induction of cell death, PS is externalized on the outer surface via the activation of phospholipid scramblases. Externalized PS not only changes the biochemical and biophysical properties of the plasma membrane but also initiates a series of interactions between endogenous extracellular proteins as well as receptors on neighboring cells to stimulate engulfment (efferocytosis) that influence the surrounding immune milieu. In this thematic series published in Cell Communication and Signaling, we feature review articles that highlight recent work in the field of PS biology, including the biochemistry and physiological significance of PS externalization, therapeutic applications and efforts to target PS, as well as posit open questions that remain in the field.

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“…Recently, Oncologie Inc. (current owner of Bavi) has announced two new clinical trials that are now recruiting and involve a combinatorial intervention of Bavi and anti-PD-1 (KEYTRUDA, Merck): Phase II Open Label Study in Advanced Gastric and GEJ Cancer Patients (NCT04099641) and Phase II Open Label Study in Advanced Hepatocellular Carcinoma (NCT03519997). The outcomes of the Bavi trials, as well as future studies developing novel PS-targeting molecules, such as the PS-binding peptide–peptoid hybrid, PPS1D1 [ 137 ]; PS-targeting nanovesicles (SapC-DOPS) [ 138 , 139 ]; and bispecific antibodies will be necessary to assess whether PS-targeting approaches will have clinical utility in immuno-oncology.…”

Section: Modulation Of Ps Signaling and Efferocytosis As An Anti-tmentioning

confidence: 99%

Cell Death in the Tumor Microenvironment: Implications for Cancer Immunotherapy

Gadiyar

Lahey

Calianese

et al. 2020

Cells

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The physiological fate of cells that die by apoptosis is their prompt and efficient removal by efferocytosis. During these processes, apoptotic cells release intracellular constituents that include purine nucleotides, lysophosphatidylcholine (LPC), and Sphingosine-1-phosphate (S1P) that induce migration and chemo-attraction of phagocytes as well as mitogens and extracellular membrane-bound vesicles that contribute to apoptosis-induced compensatory proliferation and alteration of the extracellular matrix and the vascular network. Additionally, during efferocytosis, phagocytic cells produce a number of anti-inflammatory and resolving factors, and, together with apoptotic cells, efferocytic events have a homeostatic function that regulates tissue repair. These homeostatic functions are dysregulated in cancers, where, aforementioned events, if not properly controlled, can lead to cancer progression and immune escape. Here, we summarize evidence that apoptosis and efferocytosis are exploited in cancer, as well as discuss current translation and clinical efforts to harness signals from dying cells into therapeutic strategies.

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SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

Cited by 24 publications

References 44 publications

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Biology of phosphatidylserine (PS): basic physiology and implications in immunology, infectious disease, and cancer

Cell Death in the Tumor Microenvironment: Implications for Cancer Immunotherapy

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