Abstract
Abstract
A series of murine monoclonal antibodies were generated using recombinant oncofetal antigen - immature laminin receptor protein (OFA/iLRP) as the immunogen. Several of the antibodies detected the 37kD OFA/iLRP but did not recognize the structurally related 67kD mature laminin receptor protein (LRP), as determined by western blot analysis. Additional antibodies demonstrated reactivity with both proteins. Those antibodies specific for the 37kD moiety bound to recombinant OFA/iLRP with high affinity (Kaff = 1-2 x 10-10M; Biacore technology). These antibodies also reacted with native OFA/iLRP on the surface of human tumor cells with high affinity (Kaff = 1-2 x 10-9M) but did not show significant reactivity with normal human epithelial cells or fibroblasts. In contrast, antibodies that interacted with both 37kD OFA/iLRP and 67kD mature LRP were reactive with both tumor cells and normal cells. Antibodies specific to OFA/iLRP were internalized upon binding to the target protein on human tumor cells. Two monoclonal antibodies from this group were tested for anti-tumor activity in a murine model of B-cell leukemia. BALB/c mice were injected with A20 leukemia cells either intramuscularly or intravenously. Mice were given a total of six intraperitoneal 100µg antibody injections over a two-week period following tumor initiation. Both antibodies slowed growth of the intramuscular primary tumor by approximately 45%. More importantly, in the intravenous tumor model, the treatments reduced systemic blood tumor levels by greater than 70% and suppressed liver tumor formation by up to 46%. These high affinity tumor-selective antibodies potentially provide a front-line or adjuvant therapy for hematological malignancies.
Citation Format: Shannon D. McClintock, Michael K. Dame, Muhammad N. Aslam, Saqib Ali, Randall N. Knibbs, Roscoe L. Warner, James Varani. Monoclonal antibodies specific for the oncofetal antigen - immature laminin receptor: Tumor selectivity, rapid internalization and in vivo efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2666. doi:10.1158/1538-7445.AM2014-2666