AnnexinA5 renders dead tumor cells immunogenic—implications for multimodal cancer therapies

Frey, Benjamin; Schildkopf, Petra; Rödel, Franz; Weiß, Eva-Maria; Muñoz, Luis; Herrmann, Martin; Fietkau, Rainer; Gaipl, Udo S.

doi:10.1080/15476910903204058

Cited by 10 publications

(17 citation statements)

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“…Two of the better studied therapeutic strategies of this class include recombinant Annexin V (AnxV) proteins and the PS targeting monoclonal antibody developed by Thorpe et al, and subsequently tested by Peregrine Pharmaceuticals. In the case for AnxV, early studies by Herrmann et al showed that Anx5 binds with high affinity to externalized PS on dying cells associated with tumor models, can subsequently induce improved host anti‐tumor immunity, presumably by blocking the immunosuppressive of PS as developed above . More recently, systemic administration of a series of PS targeting monoclonal antibodies have also supported PS targeting as a baseline general strategy for cancer .…”

Section: Development Of Ps Targeting Biologicals and Mabs To Neutralimentioning

confidence: 98%

Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment

Kumar

Calianese

Birge

2017

Immunological Reviews

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Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell-derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis). To this end, apoptotic cells express specific eat-me signals, such as externalized phosphatidylserine (PS), that are recognized in a specific context by receptors to initiate signaling pathways for engulfment. The importance of carefully regulated recognition and clearance pathways is evident in the spectrum of inflammatory and autoimmune disorders caused by defects in PS receptors and signaling molecules. However, in recent years, several additional cell death pathways have emerged, including immunogenic cell death, necroptosis, pyroptosis, and netosis that interweave different cell death pathways with distinct innate and adaptive responses from classical apoptosis that can shape long-term host immunity. In this review, we discuss the role of different cell death pathways in terms of their immune potential outcomes specifically resulting in specific cell corpse/phagocyte interactions (phagocytic synapses) that impinge on host immunity, with a main emphasis on tolerance and cancer immunotherapy.

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Section: Development Of Ps Targeting Biologicals and Mabs To Neutralimentioning

confidence: 98%

Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment

Kumar

Calianese

Birge

2017

Immunological Reviews

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“…The modes of cancer cell death can render local applications to a systemic outcome resulting in antitumor immune responses 3 . Besides stopping the proliferation of tumor cells and killing them, 4 the main aims of antitumor therapies are keeping residual tumor cells in check and inducing immunogenic tumor cell death and immune stimulation. We will focus on how in vivo –induced tumor cell death by RT, CT, or hyperthermia (HT) can be rendered more immunogenic, and also on innovative approaches for tumor vaccines based on autologous dead tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo– and in vivo–induced dead tumor cells as modulators of antitumor responses

Weiß

Frey

Rödel

et al. 2010

Annals of the New York Academy of Sciences

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Joint application of standard tumor therapies like radiotherapy and/or chemotherapy with immune therapy has long been considered not to fit. However, it has become accepted that immune responses may contribute to the elimination of cancer cells. We present how in vivo-induced tumor cell death by irradiation, chemotherapeutic agents, or hyperthermia can be rendered more immunogenic. High hydrostatic pressure is introduced as an innovative inactivation method for tumor cells used as vaccines. Annexin A5, being a natural occurring ligand for phosphatidylserine that is exposed by dying tumor cells, renders apoptotic tumor cells immunogenic and induces tumor regression. Combinations of irradiation with hyperthermia may also foster antitumor responses. For preparation of autologous tumor cell vaccines, high hydrostatic pressure is suitable to induce immunogenic cancer cell death. Future work will be aimed toward evaluating which combination and chronological sequence of radiotherapy, chemotherapy, hyperthermia, annexin A5, and/or autologous tumor cell vaccines will induce specific and long-lasting antitumor immunity.

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“…Our findings underpin the significance of PS as a cancer cell‐specific surface factor being a promising target candidate for selective tumor treatment. Currently, PS‐directed anti‐cancer therapy approaches are typically based on the use of annexin A5 or monoclonal antibodies such as bavituximab . Both attempts aim at shielding externalized PS on cancer cells in order to surmount its immunosuppressive effects in the tumor microenvironment .…”

Section: Discussionmentioning

confidence: 99%

Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides

Wilms

Andrä

2017

J. Pept. Sci.

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Current cancer treatment is frequently compromised by severe adverse effects on healthy cells and tissues as well as by the increasing burden of (multi-)drug resistances. Some representatives of small, amphipathic peptides known as host defense peptides possess the potential to overcome these limitations and to evolve as future anti-cancer therapeutics. Peptide NK-2, derived from porcine NK-lysin, was originally discovered due to its broad-spectrum antimicrobial activities. Today, also potent anti-cancer activity is proven and accompanied by low toxicity towards normal human cells. The molecular basis underlying this target selectivity remains rather elusive. Nevertheless, it is presumptive that preferential peptide interactions with surface factors non-abundant on healthy human cells play a key role. Here, we investigated the cytotoxicity of peptide NK-2 and structurally improved anti-cancer variants thereof against two patient-derived colorectal cancer cell lines, exposing high and low levels of phosphatidylserine on their cell surfaces, respectively. Concluding from a range of in vitro tests involving cellular as well as lipid vesicle-based methods, it is proposed that the magnitude of the accessible membrane surface charge is not a primarily decisive factor for selective peptide interactions. Instead, it is suggested that the level of membrane surface-exposed phosphatidylserine is of crucial importance for the activity of peptide NK-2 and enhanced variants thereof in terms of their cancer cell selectivity, the overall efficacy, as well as the underlying mode of action and kinetics. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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AnnexinA5 renders dead tumor cells immunogenic—implications for multimodal cancer therapies

Cited by 10 publications

References 0 publications

Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment

Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment

Ex vivo– and in vivo–induced dead tumor cells as modulators of antitumor responses

Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides

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