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.
Keywords: A20 murine B-cell leukemia; ADC, Antibody-drug conjugate; ADCC, Antibody dependent cellular cytotoxicity; ANOVA, Analysis of variance; B16 melanoma; BV, Benovus; CDC, Complement dependent cytotoxicity; ELISA, Enzyme-linked immunosorbent assay; FBS, Fetal bovine serum; IgG, Immunoglobulin G; LRP, Laminin receptor protein; OFA/iLRP, Oncofetal antigen –; RPMI, Roswell Park Memorial Institute; SCID, Severe combined immune deficiency; blood-borne metastasis; cDNA, complementary DNA; immature laminin receptor protein; kD, kilo Dalton; mRNA, messenger RNA.