99mTc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials

Belhocine, Tarik; Blankenberg, Francis G.; Kartachova, Marina; Stitt, Larry; Vanderheyden, Jean-Luc; Hoebers, Frank; Wiele, Christophe Van de

doi:10.1007/s00259-015-3152-0

Cited by 41 publications

(27 citation statements)

References 68 publications

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“…This study reports the potential of targeting tumor PS as an effective approach to enhance the immunogenicity of the TME and immunotherapy for the generation of potent antitumor immunity. Due to the current application of AnxA5 as tumor imaging tools in clinical studies 61 , such approaches have high clinical feasibility and translational potential and may lead to the development of novel and readily adaptable immunotherapeutic for the treatment of cancer.…”

Section: Cis Onlymentioning

confidence: 99%

Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment

et al. 2020

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The interaction between immune cells and phosphatidylserine (PS) molecules exposed on the surface of apoptotic-tumor bodies, such as those induced by chemotherapies, contributes to the formation of an immunosuppressive tumor microenvironment (TME). Annexin A5 (AnxA5) binds with high affinity to PS externalized by apoptotic cells, thereby hindering their interaction with immune cells. Here, we show that AnxA5 administration rescue the immunosuppressive state of the TME induced by chemotherapy. Due to the preferential homing of AnxA5 to the TME enriched with PS+ tumor cells, we demonstrate in vivo that fusing tumor-antigen peptide to AnxA5 significantly enhances its immunogenicity and antitumor efficacy when administered after chemotherapy. Also, the therapeutic antitumor effect of an AnxA5-peptide fusion can be further enhanced by administration of other immune checkpoint inhibitors. Our findings support the administration of AnxA5 following chemotherapy as a promising immune checkpoint inhibitor for cancer treatment.

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Section: Cis Onlymentioning

confidence: 99%

Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment

et al. 2020

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“…Notably, in particular primary tumor cell cultures and metastases have been shown to predominantly express PS without being in an apoptotic state; the same applies for cells of the tumor vasculature . In multimodal tumor treatment concepts, one could have on the radar to exploit the capability of AnxA5 or other members of this protein family for targeting aggressive tumor cells and for induction of necrosis and secondary necrosis by blocking the removal of PS‐exposing irradiated tumor cells, despite its use for imaging tumor responses to treatments …”

Section: Impact Of Radiation and Additional Immune Modulators On The mentioning

confidence: 99%

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

Frey

Rückert

Deloch

et al. 2017

Immunological Reviews

152

127

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Ionizing radiation is often regarded as an element of danger. But, danger responses on the cellular and molecular level are often beneficial with regard to the induction of anti-tumor immunity and for amelioration of inflammation. We outline how in dependence of radiation dose and fraction, radiation itself-and especially in combination with immune modulators-impacts on the innate and adaptive immune system. Focus is set on radiation-induced changes of the tumor cell phenotype and the cellular microenvironment including immunogenic cancer cell death. Mechanisms how anti-tumor immune responses are triggered by radiotherapy in combination with hyperthermia, inhibition of apoptosis, the adjuvant AnnexinA5, or vaccination with high hydrostatic pressure-killed autologous tumor cells are discussed. Building on this, feasible multimodal radio-immunotherapy concepts are reviewed including overcoming immune suppression by immune checkpoint inhibitors and by targeting TGF-β. Since radiation-induced tissue damage, inflammation, and anti-tumor immune responses are interconnected, the impact of lower doses of radiation on amelioration of inflammation is outlined. Closely meshed immune monitoring concepts based on the liquid biopsy blood are suggested for prognosis and prediction of cancer and non-cancer inflammatory diseases. Finally, challenges and visions for the design of cancer radio-immunotherapies and for treatment of benign inflammatory diseases are given.

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“…Annexin A5 is commonly used for detection of apoptotic cells by its ability to interact with phosphatidylserine, a known marker of cell apoptosis when it is on the outer leaflet of the plasma membrane. All functions of the protein are unknown exactly, but, annexin A5 has been proposed to play a role in the inhibition of blood coagulation due to competing for phosphotidylserine binding sites with as well as to inhibit the activity of phospholipase A1 [52]. Protein disulfide isomerase catalyzes the formation and breakage of disulfide within proteins as they fold [53].…”

Section: Page 7 Ofmentioning

confidence: 99%

Identification of Major Proteins of a Very Stable High Molecular Mass Multi-Protein Complex of Human Placental Tissue Possessing Nine Different Catalytic Activities

Burkova¹,

Dmitrenok²,

Bulgakov³

et al. 2018

Biochem Anal Biochem

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Human placenta is an organ protecting, feeding, and regulating the grooving of the embryo. Therefore, identification and characterization of placental components including proteins and their multi-protein complexes is an important step to understanding the placenta function. Here we analyzed for the first time human placentas extremely stable multi-protein complex (SPC, ~1000 kDa) by MALDI MS and MS/MS spectrometry using proteins tryptic hydrolyzates after proteins separation by SDS-PAGE and 2-D electrophoresis. The formation of such a very stable complex due to the random association of several various proteins is very unlikely. It was shown that SPCs contain twelve proteins: hemoglobin, alkaline phosphatase, cytoplasmic actin, human serum albumin, chorionic somatomammotropin hormone, heat shock protein beta-1, peroxiredoxin-1, 78 kDa glucose-regulated protein, protein disulfide isomerase A3, serotransferrin, annexin A5, and IgGs. These twelve proteins have in themselves many different and important biological functions, which can be inherent for these proteins in the complex. In addition, the complex demonstrated nine different enzymatic activities: DNase, RNase, ATPase, phosphatase, protease, amylase, catalase, peroxidase (H 2 O 2-dependent) and oxidoreductase (H 2 O 2-independent). The efficiency of the catalysis of each of these reactions by SPC preparations from three placentas was comparable. It was shown that hydrolysis of r(pU)23, r(pA)23, and r(pC)23 leads to the formation of 1-22-mer oligonucleotides, while digestion of microRNA mirR137 is a site-specific (3A-4U > 9U-10A > 8U-9U ≥ 15U-16A) resulting in the formation of only four major products. A large number of potentially possible functions of the complex in accordance with the functions of its individual proteins are considered. Progress in the study of placental proteins complexes can promote understanding of their biological functions.

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99mTc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials

Cited by 41 publications

References 68 publications

Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment

Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

Identification of Major Proteins of a Very Stable High Molecular Mass Multi-Protein Complex of Human Placental Tissue Possessing Nine Different Catalytic Activities

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