Monoclonal antibodies specific for oncofetal antigen--immature laminin receptor protein: Effects on tumor growth and spread in two murine models

针对癌胚抗原-未成熟层粘连蛋白受体蛋白的单克隆抗体:对两种小鼠模型中肿瘤生长和扩散的影响

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作者:Shannon D McClintock, Roscoe L Warner, Saqib Ali, Apurupa Chekuri, Michael K Dame, Durga Attili, Randall K Knibbs, Muhammad Nadeem Aslam, Joseph Sinkule, Alton Charles Morgan, Adel Barsoum, Lauren B Smith, David G Beer, Kent J Johnson, James Varani

Abstract

The oncofetal antigen - immature laminin receptor protein (OFA/iLRP) has been linked to metastatic tumor spread for several years. The present study, in which 2 highly-specific, high-affinity OFA/iLRP-reactive mouse monoclonal antibodies were examined for ability to suppress tumor cell growth and metastatic spread in the A20 B-cell leukemia model and the B16 melanoma model, provides the first direct evidence that targeting OFA/iLRP with exogenous antibodies can have therapeutic benefit. While the antibodies were modestly effective at preventing tumor growth at the primary injection site, both antibodies strongly suppressed end-organ tumor formation following intravenous tumor cell injection. Capacity of anti-OFA/iLRP antibodies to suppress tumor spread through the blood in the leukemia model suggests their use as a therapy for individuals with leukemic disease (either for patients in remission or even as part of an induction therapy). The results also suggest use against metastatic spread with solid tumors.

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