CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model

Abstract

Background: The completeness of resection is a key prognostic indicator in patients with ovarian cancer, and the application of tumour-targeted fluorescence image-guided surgery (FIGS) has led to improved detection of peritoneal metastases during cytoreductive surgery. CD24 is highly expressed in ovarian cancer and has been shown to be a suitable biomarker for tumour-targeted imaging. Methods: CD24 expression was investigated in cell lines and heterogenous patient-derived xenograft (PDX) tumour samples of high-grade serous ovarian carcinoma (HGSOC). After conjugation of the monoclonal antibody CD24 to the NIR dye Alexa Fluor 750 and the evaluation of the optimal pharmacological parameters (OV-90, n = 21), orthotopic HGSOC metastatic xenografts (OV-90, n = 16) underwent cytoreductive surgery with real-time feedback. The impact of intraoperative CD24-targeted fluorescence guidance was compared to white light and palpation alone, and the recurrence of disease was monitored post-operatively (OV-90, n = 12). CD24-AF750 was further evaluated in four clinically annotated orthotopic PDX models of metastatic HGSOC, to validate the translational potential for intraoperative guidance. Findings: CD24-targeted intraoperative NIR FIGS significantly (473%) improved tumour detection and resection, and reduced the post-operative tumour burden compared to standard white-light surgery in orthotopic HGSOC xenografts. CD24-AF750 allowed identification of minuscule tumour lesions which were undetectable with the naked eye in four HGSOC PDX. Interpretation: CD24-targeted FIGS has translational potential as an aid to improve debulking surgery of ovarian cancer.

Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells

“…Previous reports have showed CD24 is a potential oncogene and overexpressed in a large variety of human malignancies ( 44 ). Many efforts have been done for early intervention about CD24 target in the prevention and treatment of cancer, such as colorectal cancer, pancreatic cancer ( 45 ), ovarian cancer ( 46 ) and bladder cancer ( 47 ). It seems promising that the therapeutic potential of CD24 blockade with monoclonal antibodies, which may promote the phagocytic clearance of CD24 + cancer cells both in vitro and in vivo ( 20 ).…”

The Emerging Role of CD24 in Cancer Theranostics—A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond

“…As a result, CD24 overexpression has been exploited as a diagnostic marker and as a marker for treatment resistance and prognosis, and evaluated for targeted therapy [17,60,61]. In recent years, CD24 has evolved as an encouraging molecular biomarker for EOC [78] in the field of immunotherapy, and as a tumor-specific biomarker for targeted drug delivery and imaging [14,16,19]. CD24 expression in ovarian cancer has been found to correlate with clinicopathological parameters, such as higher tumor grade, higher tumor stage, omental metastasis, relapse, and a more aggressive course of the disease [17,66,79].…”

“…For real-time intraoperative fluorescence imaging, conjugation to the NIR dye Alexa Fluor 750 improved its optical properties by allowing deeper tissue penetration along with low tissue autofluorescence. FIGS enabled the intraoperative identification of the primary tumor and miniscule metastases in seven heterogeneous CD24-expressing PDX models, and ultimately improved tumor resection in preclinical orthotopic PDX [ 14 ]. CD24’s monoclonal antibody-based fluorescence intensity peaked 48 h after injection.…”

“…Cluster of differentiation 24 (CD24) is a novel molecular target used for imaging, molecular-targeted drug therapy, and immunotherapy [ 14 , 15 , 16 ]. Its high expression on tumor cells and rare expression on healthy human tissue, where it is primarily found on hematologic cells, indicate its potential as a tumor-specific biomarker [ 14 , 15 , 16 ]. A meta-analysis of 28 studies revealed that CD24 is overexpressed in 68% of human cancers, and CD24 expression was correlated with a higher self-renewal ability, more metastases, and a poor prognosis [ 17 ].…”

“…In EOC, CD24 is almost uniformly (70.1–100%) expressed [ 18 , 19 ]. We have demonstrated the ability of a CD24-targeting mAb conjugated with near-infrared (NIR) fluorophores to identify tumor lesions in metastatic EOC patient-derived xenograft (PDX) models with heterogeneous CD24 expression, supporting its potential to translate CD24-guidance to the intraoperative setting for EOC patients [ 14 , 19 ]. Here, we review the emerging tumor-specific biomarker CD24 as a target for FIGS, and focus specifically on EOC and the use of CD24 as a bimodal biomarker for both imaging and theranostics.…”