The Trojan Horse Tale Revisited: An Eye on Metastatic Spread of Carcinoma Cells

Grajewski, Rafael S.; Bosch, Johanna L.; Bruns, Heiko; Cursiefen, Claus; Heindl, Ludwig M.

doi:10.1158/2326-6066.cir-15-0127

Cited by 8 publications

(3 citation statements)

References 13 publications

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“…In addition, we also observed an interesting results that the cellular uptake of NPs was reduced after EM encapsulation. This was possibly because that the long circulatory effect of EM encapsulation is mainly dependent on the transmembrane protein CD 47 on the surface of EM, which can specifically recognize the signal regulatory protein α (SIRP-α) on the surface of macrophages to avoid the phagocytosis of EM-coated NPs [27,28]. Interestingly, SIRP-α is also expressed on the surface of HeLa tumor cells [29], which should be responsible, at least in part, for the decreased cellular uptake of EM-coated NPs by tumor cells.…”

Section: Cellular Uptake By Hela Cellsmentioning

confidence: 99%

An effective intracellular delivery system of monoclonal antibody for treatment of tumors: erythrocyte membrane-coated self-associated antibody nanoparticles

et al. 2017

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Antibody-based drugs have attracted much attention for their targeting ability, high efficacy and low toxicity. But it is difficult for those intrabodies, a kind of antibody whose targets are intracellular biomarkers, to become effective drugs due to the lack of intracellular delivery strategy and their short circulation time in blood. Human telomerase reverse transcriptase (hTERT), an important biomarker for tumors, is expressed only in cytoplasm instead of on cell membrane. In this study, the anti-hTERT blocking monoclonal antibody (mAb), as the model intrabody, was used to prepare nanoparticles (NPs), followed by the encapsulation of erythrocyte membrane (EM), to obtain the EM-coated anti-hTERT mAb NPs delivery system. The final NPs showed a z-average hydrodynamic diameter of about 197.3 nm. The in vitro cellular uptake by HeLa cells confirmed that compared with free anti-hTERT mAb, the EM-coated anti-hTERT mAb NPs exhibited a significantly increased uptake by tumor cells. Besides, the pharmacokinetic study confirmed that the EM encapsulation can remarkably prolong the circulation time and increase the area under curve (AUC) of NPs in blood. The EM-coated anti-hTERT mAb NPs exhibited a remarkably decreased uptake by macrophages than uncoated NPs, which may be responsible for the prolonged circulation time and increased AUC. Furthermore, the frozen section of tumor tissue was performed and proved that the EM-coated anti-hTERT mAb NPs can be more effectively accumulated in tumor tissues than the free mAb and uncoated NPs. In summary, this study indicated that EM-coated anti-hTERT mAb NPs are an effective delivery system for the long circulation and intracellular delivery of an intrabody, and make it possible for the intracellular biomarkers to become the potential targets of drugs.

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Section: Cellular Uptake By Hela Cellsmentioning

confidence: 99%

An effective intracellular delivery system of monoclonal antibody for treatment of tumors: erythrocyte membrane-coated self-associated antibody nanoparticles

et al. 2017

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“…Wir konnten zeigen, dass sich tumorinduzierte Lymphgefäße und melanomassoziierte Immunzellinfiltrate, insbesondere Makrophagen und T-Lymphozyten, im murinen Tumorgewebe in unmittelbarer Nachbarschaft befinden [25]. Diese stromale Interaktion beobachteten wir nicht nur im Tiermodell, sondern auch im gesunden Humangewebe des Auges sowie klinisch bei einem Patienten mit intraokulärer Metastase [26][27][28]. Wie und ob sie einander beeinflussen, ist noch nicht vollständig geklärt.…”

Section: Lymphangiogenese Und Immunzellinfiltration Beim Okulären Melunclassified

Neue adjuvante Therapien beim okulären Melanom

Bosch

Heindl

2017

Klin Monatsbl Augenheilkd

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Malignant melanoma is the most common cancer of the eye in adults that originates either in the intra-ocular uveal tract or extra-ocular conjunctiva. Although the primary tumor can be treated successfully, no effective therapy for both metastatic conjunctival and uveal melanoma currently exits. Tumor-associated lymphangiogenesis and immune cell infiltration play a pivotal role in the development and therapeutic targeting of metastases. Here, we provide an overview of current translational research on lymphangiogenesis and its therapeutic inhibition as well as modulation of immune cell infiltration by passive and active immunotherapy in melanoma of the eye. Specifically, our previous and ongoing work on lymphangiogenesis and immune cells in ocular melanoma within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye" is summarized. Translational research on the modulation of tumor-associated lymphangiogenesis and immune cell infiltration could provide novel targets for adjuvant therapy in melanoma of the eye.

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“…B. im Bereich der Aderhaut [1]. Ein karzinombedingtes Pseudohypopyon gilt derzeit als absolute Rarität und wurde ohne weitere solide Metastasierung lediglich in einzelnen Kasuistiken wie der von Wunderlich et al und zuletzt auch von uns beschrieben [2]. In unserem Fall war das Geschehen sogar nur auf die Vorderkammer beschränkt, ohne nachweisbare Glaskörperzellen.…”

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