SGM-101 in Colorectal Lung Metastasis (SGMCLM)
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Lung Metastases
PROVIDER: 2442287 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Primary objectives: 1. To determine the feasibility of SGM-101 for intraoperative imaging of colorectal lung metastases - Concordance between fluorescent signal and tumor status of resected tissue
Primary endpoints: Concordance between intraoperative fluorescence assessment of resected lesions and their histopathology in terms of both CEA expression and tumor status.
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Project description:This study assesses the feasibility of SGM-101, a fluorochrome-labeled anti-carcinoembryonic antigen monoclonal antibody, for intraoperative near-infrared fluorescence imaging of colorectal brain metastases by injecting SGM-101 intravenously 3 - 5 days prior to surgery.
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Project description:Near-infrared fluorescence-guided oncologic surgery (FGOS) with the use of a tumor specific tracer (SGM-101) developed by Surgimab can provide valuable intra-operative information about tumor location and extensiveness. SGM-101 already proven to be safe and valuable in colorectal cancer.
This study aims to prove feasibility for colorectal lung metastases.
| 2366037 | ecrin-mdr-crc
Project description:PurposeMetastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during minimally invasive surgery. Intraoperative fluorescence imaging has the potential to overcome these challenges. The aim of this study was to assess feasibility of targeting CLM with the carcinoembryonic antigen (CEA) specific fluorescent tracer SGM-101.MethodsThis was a prospective, open-label feasibility study. The primary outcome was the number of CLM that showed a true positive fluorescence signal with SGM-101. Fluorescence positive signal was defined as a signal-to-background ratio (SBR) ≥ 1.5. A secondary endpoint was the CEA expression in the colorectal lung metastases, assessed with the immunohistochemistry, and scored by the total immunostaining score.ResultsThirteen patients were included in this study. Positive fluorescence signal with in vivo, back table, and closed-field bread loaf imaging was observed in 31%, 45%, and 94% of the tumors respectively. Median SBRs for the three imaging modalities were 1.00 (IQR: 1.00-1.53), 1.45 (IQR: 1.00-1.89), and 4.81 (IQR: 2.70-7.41). All tumor lesions had a maximum total immunostaining score for CEA expression of 12/12.ConclusionThis study demonstrated the potential of fluorescence imaging of CLM with SGM-101. CEA expression was observed in all tumors, and closed-field imaging showed excellent CEA specific targeting of the tracer to the tumor nodules. The full potential of SGM-101 for in vivo detection of the tracer can be achieved with improved minimal invasive imaging systems and optimal patient selection.Trial registrationThe study was registered in ClinicalTrial.gov under identifier NCT04737213 at February 2021.
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Project description:Rationale: Extracellular vesicles (EVs) have emerged as novel mediators of cell-to-cell communication that are capable of the stable transfer of therapeutic microRNAs (miRNAs), and thus, EVs hold immense promise as a miRNA delivery system for cancer therapy. Additionally, as miRNA-containing EVs are secreted into circulation, miRNAs contained within plasma EVs may represent ideal biomarkers for diseases. The objective of this study was to characterize a potential tumor suppressor miRNA, miR-101, and explore the potential of miR-101 delivery via EVs for in vivo therapy of metastatic osteosarcoma as well as the potential value of plasma EV-packaged miR-101 (EV-miR-101) level for predicting osteosarcoma metastasis. Methods: The relationship of miR-101 expression and osteosarcoma progression was investigated in osteosarcoma specimens by in situ hybridization (ISH), and the potential inhibitory effect of miR-101 was further investigated using in vivo models. Using prediction software analysis, the mechanism of action of miR-101 in osteosarcoma was explored using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting and dual-luciferase assay. Adipose tissue-derived mesenchymal stromal cells (AD-MSCs) were transduced with lentiviral particles to obtain miR-101-enriched EVs. A Transwell assay and lung metastasis models of osteosarcoma were used to observe the effect of miR-101-enriched EVs on osteosarcoma invasiveness and metastasis. Detection of plasma EV-miR-101 levels was carried out in osteosarcoma patients and healthy controls by qRT-PCR. Results: miR-101 expression was markedly lower in metastatic osteosarcoma specimens compared to non-metastatic specimens. Significantly fewer metastatic lung nodules were formed by Saos-2 cells overexpressing miR-101 and SOSP-9607 cells overexpressing miR-101 injected into mice. With increased miR-101 expression, B cell lymphoma 6 (BCL6) mRNA and protein expression levels were reduced, and miR-101 was found to exert its effects by directly targeting BCL6. AD-MSCs were successfully engineered to secrete miR-101-enriched EVs. Once taken up by osteosarcoma cells, these EVs showed suppressive effects on cell invasion and migration in vitro, and systemic administration of these EVs effectively suppressed metastasis in vivo with no significant side effects. Finally, the EV-miR-101 level was lower in osteosarcoma patients than in healthy controls and even lower in osteosarcoma patients with metastasis than in those without metastasis. Conclusion: Our data support the function of miR-101 as a tumor suppressor in osteosarcoma via downregulation of BCL6. AD-MSC derived miR-101-enriched EVs represent a potential innovative therapy for metastatic osteosarcoma. EV-miR-101 also represents a promising circulating biomarker of osteosarcoma metastasis.
| S-EPMC6929625 | biostudies-literature
Project description:BackgroundCarcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC.MethodsPatients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose.ResultsThirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients.ConclusionsThe optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.
| S-EPMC7892528 | biostudies-literature
Project description:The real-time improvement of the intraoperative discrimination between different tissue types (particularly between tumor and adjacent normal tissue) using intraoperative imaging represents a considerable advance for oncology surgeons. However, the development of imaging agents is much slower than that of drug therapies, although surgery represents one of the few curative treatments for many solid tumors. SGM-101 is a recently described, innovative antibody conjugate in which the near-infrared fluorochrome BM-104 is covalently linked to a chimeric monoclonal antibody against carcinoembryonic antigen (CEA). SGM-101 was developed with the goal of providing oncology surgeons with an intraoperative imaging tool that allows the visualization of CEA-overexpressing tumors. This antigen is overexpressed in a wide range of human carcinomas, such as colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Here we characterized SGM-101 safety prior to its clinical testing for real-time cancer mapping by oncology surgeons. Safety pharmacology and toxicology studies were performed after intravenous injection of SGM-101 in Wistar rats and in Beagle dogs. SGM-101 metabolism and pharmacokinetics were analyzed in rats and mice. Finally, the potential toxicity of the BM-104 dye and SGM-101 cross-reactivity were assessed in a panel of 42 human tissues. Our pre-clinical toxicology, pharmacology and pharmacokinetic results demonstrated the absence of significant adverse effects of both SGM-101 and BM-104 at doses well above the anticipated maximal human exposure. Taken together, the results of the pharmacology, pharmacokinetic and toxicology studies support the development of SGM-101 as a potentially useful and safe tumor-specific imaging tool that might improve the complete tumor resection rate.
| S-EPMC6506861 | biostudies-literature
Project description:The performance of SGM-101, an intraoperative imaging agent, will be compared to that of standard "white light" visualization during surgical resections of colorectal cancer.
| 2283240 | ecrin-mdr-crc
Project description:Clinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC), and the treatment outcome of metastatic NPC remains disappointing, so there is a pressing need to identify novel therapeutic strategies. In accordance with our previous microarray data, we found that miR-101 was downregulated in NPC clinical specimens and cell lines. Ectopic expression of miR-101 significantly suppressed NPC cell migration, invasion and angiogenesis in vitro and inhibited angiogenesis and metastasis in vivo using the chicken chorioallantoic membrane model. Furthermore, ITGA3 was identified and validated as a novel target of miR-101, and the restoration of ITGA3 expression potently rescued the suppressive effects of miR-101. In addition, NPC patients with high ITGA3 expression had poorer overall survival and distant metastasis-free survival than patients with low ITGA3 expression, and ITGA3 overexpression was an independent poor prognostic factor in NPC. More importantly, we demonstrated that the systemic delivery of lentivirus-mediated miR-101 abrogated the lung metastatic colonization formation of NPC cells without obvious toxicity. Our study elucidates the molecular mechanisms of miR-101/ITGA3 pathway in regulating NPC metastasis and angiogenesis, and the systemic delivery of miR-101 provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for NPC patients.
| S-EPMC5386386 | biostudies-literature
Project description:BackgroundNear-infrared (NIR) fluorescence is a promising novel imaging technique that can aid in intraoperative demarcation of pancreatic cancer (PDAC) and thus increase radical resection rates. This study investigated SGM-101, a novel, fluorescent-labeled anti-carcinoembryonic antigen (CEA) antibody. The phase 1 study aimed to assess the tolerability and feasibility of intraoperative fluorescence tumor imaging using SGM-101 in patients undergoing a surgical exploration for PDAC.MethodsAt least 48 h before undergoing surgery for PDAC, 12 patients were injected intravenously with 5, 7.5, or 10 mg of SGM-101. Tolerability assessments were performed at regular intervals after dosing. The surgical field was imaged using the Quest NIR imaging system. Concordance between fluorescence and tumor presence on histopathology was studied.ResultsIn this study, SGM-101 specifically accumulated in CEA-expressing primary tumors and peritoneal and liver metastases, allowing real-time intraoperative fluorescence imaging. The mean tumor-to-background ratio (TBR) was 1.6 for primary tumors and 1.7 for metastatic lesions. One false-positive lesion was detected (CEA-expressing intraductal papillary mucinous neoplasm). False-negativity was seen twice as a consequence of overlying blood or tissue that blocked the fluorescent signal.ConclusionThe use of a fluorescent-labeled anti-CEA antibody was safe and feasible for the intraoperative detection of both primary PDAC and metastases. These results warrant further research to determine the impact of this technique on clinical decision making and overall survival.
| S-EPMC6132431 | biostudies-literature