Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal,antigen and receptor for Wnt5a

作者：Fukuda Tetsuya; Chen Liguang; Endo Tomoyuki; Tang Li; Lu Desheng; Castro Jariuario E; Widhopf George F II; Rassenti Laura Z; Cantwell Mark J; Prussak Charles E; Carson Dennis A^*; Kipps Thomas J

来源：Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(8): 3047-3052.

DOI：10.1073/pnas.0712148105

• chronic lymphocytic leukemia
• neoplasia

We examined the sera of six patients before and after i.v. infusions of autologous chronic lymphocytic leukemia (CLL) cells transduced ex vivo with an adenovirus encoding CD154 (Ad-CD154). Five patients made high-titer antibodies against adenovirus and three made IgG reactive with a leukemia-associated surface antigen, which we identified as ROR1. Anti-ROR1 antibodies were not detected in the sera of untreated patients. We generated anti-ROR1 mAbs and found they reacted specifically with the CLL cells of all patients, but not with nonleukemic leukocytes, a wide variety of normal adult tissues, or blood mononuclear cells, including CD5(+) B cells of healthy adults. ROR1 could bind Wnt5a, which induced activation of NF-kappa B when coexpressed with ROR1 in HEK293 cells and enhanced the survival of CLL cells in vitro, an effect that could be neutralized by posttreatment anti-ROR1 antisera. We conclude that patients with CLL can break immune tolerance to ROR1, which is an oncofetal surface antigen and survival-signaling receptor in this neoplastic disease.

• 出版日期2008-2-26