scholarly journals Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5446
Author(s):  
Elisa C. Toffoli ◽  
Abdolkarim Sheikhi ◽  
Roeland Lameris ◽  
Lisa A. King ◽  
Amanda van Vliet ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Nk Cells ◽  
Tumor Cells ◽  
Nk Cell ◽  
Growth Factor Receptor ◽  
Single Domain Antibody ◽  
Domain Antibody ◽  
Epidermal Growth

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin. The bispecific VHH triggered CD16- and EGFR-dependent activation of NK cells and subsequent lysis of tumor cells, regardless of the KRAS mutational status of the tumor. Enhancement of NK cell activation by the bispecific VHH was also observed when NK cells of colorectal cancer (CRC) patients were co-cultured with EGFR expressing tumor cells. Finally, higher levels of cytotoxicity were found against patient-derived metastatic CRC cells in the presence of the bispecific VHH and autologous peripheral blood mononuclear cells or allogeneic CD16 expressing NK cells. The anticancer activity of CD16-EGFR bispecific VHHs reported here merits further exploration to assess its potential therapeutic activity either alone or in combination with adoptive NK cell-based therapeutic approaches.

scholarly journals Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers

2018 ◽  
Vol 129 (3) ◽  
pp. 805-814 ◽  
Author(s):  
Eric D. Young ◽  
Davis Ingram ◽  
William Metcalf-Doetsch ◽  
Dilshad Khan ◽  
Ghadah Al Sannaa ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Peripheral Nerve ◽  
Tumor Cells ◽  
Tissue Microarray ◽  
Growth Factor Receptor ◽  
Nerve Sheath ◽  
Epidermal Growth

OBJECTIVEWhile sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS.METHODSPatients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121).RESULTSSPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor–β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor–2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018).CONCLUSIONSComplete resection is curative for SPS. Left untreated, however, these tumors can cause significant morbidity, and not all patients are candidates for resection. SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2–associated schwannomas, suggesting a shared etiology. This SPS pattern is distinct from that of other tumors of the peripheral nerve sheath.

scholarly journals Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity

2020 ◽  
Author(s):  
Lei Wang ◽  
Xusha Zhou ◽  
Weixuan Zou ◽  
Yinglin Wu ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Growth Factor Receptor ◽  
Wide Range ◽  
Epidermal Growth

Abstract Background: Exosomes are small, cellular membrane-derived vesicles with a diameter of 50-150 nm. Exosomes are considered ideal drug delivery systems with a wide range of applications in various diseases, including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains challenging. H uman epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase, and its overexpression is usually associated with cell survival and tumor progression in various cancers. In this study, we aim to develop novel exosomes with dual HER2-targeting ability as a nanoparticle delivery vehicle to enhance antitumor efficacy in vivo . Results: Here, we report the generation of two kinds of exosomes carrying miRNAs designed to block HER2 synthesis and consequently kill tumor cells. 293-miR-HER2 exosomes package and deliver designed miRNAs to cells to block HER2 synthesis. These exosomes kill cancer cells dependent on HER2 for survival but do not affect cells that lack HER2 or that are engineered to express HER2 but are not dependent on it for survival. In contrast, 293-miR-XS-HER2 exosomes carry an additional peptide, which enables them to adhere to HER2 on the surface of cancer cells. Consequently, these exosomes preferentially enter and kill cells with surface expression of HER2. 293-miR-XS-HER2 exosomes are significantly more effective than the 293-miR-HER2 exosomes in shrinking HER2-positive tumors implanted in mice. Conclusions: Collectively, as novel antitumor drug delivery vehicles, HER2 dual-targeting exosomes exhibit increased target-specific delivery efficiency and can be further utilized to develop new nanoparticle-based targeted therapies.

scholarly journals Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma

PRILOZI ◽  
2018 ◽  
Vol 39 (2-3) ◽  
pp. 21-28
Author(s):  
Dafina Nikolova ◽  
Viktorija Chalovska ◽  
Magdalena Genadieva Ivanova ◽  
Emilija Nikolovska ◽  
Ance Volkanovska ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tumor Cells ◽  
Liver Tissue ◽  
Vascular Invasion ◽  
Tumor Tissue ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Abstract Introduction: Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. Material and Methods: We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival. Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. Results: Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51. Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months. The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors. EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00). Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly. Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly. EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05). Conclusion: The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

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