Anti-Lewis Y Antibody As a Novel Target for Pancreatic Adenocarcinoma
Vivian E. Strong*1, Achim a. Jungbluth3, Peter J. Allen1, Laura H. Tang4, Lloyd Old3, Steven Larson2, Jorge Carrasquillo2, Yuman Fong1
1Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY; 2Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; 3Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY; 4Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY
Lewis Y antigen is a blood group antigen homogeneously expressed at high density on the surface of various tumor cells. Hu3S193 is a specific antibody against Lewis Y antigen and this antibody has shown exceptionally high specificity for Lewis Y antigen with no cross-reactivity and potent immune effector function. This study evaluated Lewis Y expression in pancreatic adenocarcinoma.Human tissue samples (n=43) from paraffin embedded blocks were evaluated via immunohistochemical (IHC) staining with 3S193 antibody. An antigen retrieval technique was performed by immersing slides in preheated DAKO-TRS solution and ultimate detection with avidin biotin system. Binding was graded by review of two dedicated pathologists who were blinded as to the clinical history of each specimen. Grading was categorized as negative, focally positive or graded % binding. IHC staining of human pancreas tissue shows intense uptake of 3S193 antibody in regions consistent with pancreas adenocarcinoma (panel A). In contrast, panel B demonstrates minimal IHC staining of normal pancreatic tissue. Table 1 shows results of IHC staining for 55 human pancreas adenocarcinoma specimens with 80% showing strong staining. The results of this study demonstrate the up-regulation of Lewis Y antigen in pancreatic adenocarcinoma, and the targeting capability of Hu3S193. These results may allow the development of better imaging and novel therapies to specifically target pancreatic adenocarcinoma.
Table 1. Immunohistochemical (IHC) staining from human pancreas cancer specimens
| Amt of Staining via Immunohistochemistry for Hu3S193 Antibody | Number of Pancreas Adenocarcinoma Specimens | Percentage of Total Specimens (n=55) |
| Negative | 11 | 20% |
| Focally Positive | 3 | 5% |
| 5-25% | 13 | 24% |
| 25-50% | 9 | 16% |
| 50-75% | 8 | 15% |
| 75-100% | 11 | 20% |
| Total | 55 | 100% |
| Total Positive | 44 | 80% |
In 80% of all specimens examined (44/55) there was detectable staining of cancer cells with the anti-lewis Y antibody.
3S193 immunostaining of pancreas adenocarcinoma (panel A) versus normal pancreas tissue (panel B). Brown regions represent positive staining for Lewis Y antigen.
