Comparative immunohistochemistry of L19 and F16 in non-small cell lung cancer and mesothelioma: Two human antibodies investigated in clinical trials in patients with cancer
Friday, September 19th, 2008.
Lung Cancer. 2008 Sep 15. [Epub ahead of print] [Link]
Pedretti M, Soltermann A, Arni S, Weder W, Neri D, Hillinger S.
Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Abstract
The antibody-mediated targeted delivery of therapeutics to tumor sites is an attractive avenue for combating cancer while sparing normal tissues. Indeed, five derivatives of the human monoclonal antibodies L19 and F16, specific to splice isoforms of fibronectin and tenascin-C, are currently being investigated in clinical trials in patients with malignancies. Until now, a comparative immunohistochemical analysis of these antibodies, which recognize components of the modified extracellular matrix, was missing. Here, we report that the majority of NSCLC and mesothelioma specimens are stained with both antibodies in the stroma, while non-tumoral lung and mesothelium samples rarely exhibit reactivity with either L19 or F16. In our analysis, the anti-tenascin F16 antibody was found to generally exhibit a stronger staining of desmoplastic stroma surrounding tumor. This superior performance was found to be particularly striking in the case of low-grade non-small cell lung cancer.
Keywords: Therapeutic antibodies; Extra-domain B of fibronectin; Extra-domain A1 of tenascin-C; Non-small cell lung cancer; Mesothelioma; Tumor-targeting
Glossary
- monoclonal antibodies
- antibodies made in the laboratory and designed to target specific substances called antigens. Monoclonal antibodies which have been attached to chemotherapy drugs or radioactive substances are being studied to see if they can seek out antigens unique to cancer cells and deliver these treatments directly to the cancer, thus killing the cancer cells without harming healthy tissue. Monoclonal antibodies are also used in other ways, for example, to help find and classify cancer cells.
- grade
- The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.
- cell
- the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- antibody
- a protein in the blood that defends against foreign agents, such as bacteria. These agents contain certain substances called antigens. Each antibody works against a specific antigen. (See also antigen.)
- tumor
- an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
