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FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxins.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Du, Xing Nagata, Satoshi Ise, Tomoko Stetler-Stevenson, Maryalice Pastan, Ira |
| Copyright Year | 2008 |
| Abstract | FCRL1 (Fc receptor-like 1) is a cell-surface membrane protein belonging to FCRL family and is preferentially expressed on B cells. To evaluate FcRL1 as an immunotherapy target for B-cell malignancies, we prepared anti-FCRL1 mAbs without cross-reactivity to other FCRL family proteins and analyzed FCRL1 protein expression on malignant cells from patients and on B-cell lines. Frequent FCRL1 expression was observed by flow cytometry on 12 B-cell non-Hodgkin lymphoma (B-NHL) cell lines and many patient samples: 12 of 14 chronic lymphocytic leukemia (CLL), 7 of 7 follicular lymphoma (FL), 13 of 17 hairy cell leukemia (HCL), and 2 of 3 mantle cell lymphoma (MCL). Two recombinant immunotoxins, E3(Fv)-PE38 and E9(Fv)-PE38, were constructed. Both immunotoxins bound to FCRL1-positive cells with similar affinities (3.4 and 3.2 nM) and were cytotoxic to cell lines, but E9(Fv)-PE38 was 4- to 20-fold more cytotoxic than E3(Fv)-PE38. The concentrations that inhibited response by 50% (IC(50)s) of E9(Fv)-PE38 on 11 different FCRL1-positive cell lines ranged from 1.0 ng/mL to 90 ng/mL and correlated with the FCRL1 expression levels. Our results suggest that anti-FCRL1 immunotoxin E9(Fv)-PE38 exhibits remarkably specific cytotoxicity and merits further evaluation for the treatment of FCRL1-positive malignancies, including CLL, HCL, FL, MCL, and other B-NHL. |
| Starting Page | 399 |
| Ending Page | 407 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/111/1/338.full.pdf?sso-checked=true |
| PubMed reference number | 17895404v1 |
| Volume Number | 111 |
| Issue Number | 1 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | B-Lymphocytes CD30 Immunotoxin Chronic Lymphocytic Leukemia Cultured Cell Line Exhibits as Topic FCRL1 gene FCRL1 protein, human Fc Receptor Flow Cytometry Hairy Cell Leukemia Hematologic Neoplasms Immunotherapy Immunotoxins Lymphoid leukemia Lymphoma, Follicular Lymphoma, Non-Hodgkin Malignant lymphoma, lymphocytic, intermediate differentiation, diffuse Membrane Proteins Patients Recombinants cancer cell protein expression |
| Content Type | Text |
| Resource Type | Article |
