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Updated: Aug 8, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
A new anticancer glycolipid monoclonal antibody, SC104, which directly induces tumor cell apoptosis
Lindy G Durrant1, Stephen J Harding, Nicola H Green
1Institute of Infections, Immunity, and Inflammation, Cancer Research UK Department of Clinical Oncology, University of Nottingham and Scancell Ltd., BioCity, Nottingham, United Kingdom. lindy.durrant@nottingham.ac.uk
Abstract:
A novel monoclonal antibody was raised by immunization of mice with colorectal tumor cell lines. The fusion was screened by immunohistochemistry for binding to primary colorectal tumors. Subsequent analysis on primary disaggregated colorectal tumors show that the antibody recognizes a cell surface antigen expressed by the majority of colorectal tumors. Antigen characterization has shown that the antibody recognizes a sialyltetraosylceramide but does not bind to GM1, GD1a, GT1b, or sialyl Lewis(X) antigens. Binding to a frozen panel of tumor and normal tissue sections revealed that the antigen was also strongly expressed on esophageal, gastric, and endometrial tumors. Its normal tissue distribution was largely restricted to moderate staining of large intestine. Surprisingly, SC104 antibody directly induces tumor cell death without the need for immune effector cells or complement. This may be related in part to its homophilic binding properties that allow cross-linking of antibody and receptors on the cell surface. Caspase activation can be detected following SC104 treatment of colorectal cells, and cotreatment with caspase inhibitors has been shown to inhibit cell death. This suggests that SC104 induces death by a classic apoptotic pathway. Furthermore, SC104 antibody shows additive killing with complement and 5-fluorouracil/leucovorin in vivo, suggesting a new therapeutic approach for this class of antibodies.
Insights
A new monoclonal antibody, SC104, targets a specific cell surface antigen on colorectal and other tumors. This antibody directly induces tumor cell death via apoptosis, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Colorectal cancer remains a significant health concern, necessitating novel therapeutic targets.
- Monoclonal antibodies have emerged as a promising class of targeted cancer therapies.
- Identifying specific tumor antigens is crucial for developing effective antibody-based treatments.
Purpose of the Study:
- To develop and characterize a novel monoclonal antibody targeting colorectal tumors.
- To investigate the antigen specificity and expression profile of the new antibody.
- To evaluate the therapeutic potential of the antibody, including its mechanism of action and in vivo efficacy.
Main Methods:
- Immunization of mice with colorectal tumor cell lines and screening via immunohistochemistry.
- Antigen characterization using various glycolipid standards and analysis of antibody binding to tumor and normal tissue sections.
- In vitro studies assessing antibody-induced tumor cell death, caspase activation, and effects of caspase inhibitors.
- In vivo studies evaluating additive effects with complement and chemotherapy (5-fluorouracil/leucovorin).
Main Results:
- A novel monoclonal antibody, SC104, was generated, recognizing a sialyltetraosylceramide cell surface antigen.
- The antigen is highly expressed on colorectal, esophageal, gastric, and endometrial tumors, with limited normal tissue distribution.
- SC104 directly induces tumor cell death through apoptosis, independent of immune effector cells or complement.
- SC104 demonstrated additive tumor cell killing in vivo when combined with complement and 5-fluorouracil/leucovorin.
Conclusions:
- SC104 represents a novel therapeutic antibody targeting a specific tumor-associated antigen.
- The antibody's ability to directly induce apoptosis and its efficacy in combination therapies suggest significant therapeutic potential for various cancers.
- SC104 offers a promising new avenue for antibody-based cancer treatment strategies.
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