Abstract 576: Immunohistochemistry and radioimaging with hJAA-11 antibody to the Thomsen-Friedenreich antigen: Potential theranostic application for breast cancer

Abstract

Abstract Theranostics through the utilization of immunohistochemistry followed by radioimaging to determine if metastatic foci will react with a therapeutic antibody will allow for the selection of the patient population that will most benefit from this immunotherapy. The Thomsen-Friedenreich antigen (TF-Ag) has been shown to be involved in ∼90% of carcinomas, specifically breast carcinomas, making it a suitable target for radioimaging and therapy. The anti-TF-Ag antibody, JAA-F11, a mouse monoclonal antibody (mAb), has had success in localization, blocking metastasis, and inhibiting cell proliferation, and binds to ∼80% of breast cancer cell lines, without preference to receptor status. This is significant since the triple negative breast cancer (ER-/PR-/HER2-) has no current targeted treatment. Studies are extended to human breast cancer tissue microarray immunohistochemical (IHC) analysis, which was scored blindly by a pathologist on a semi- quantitative scale. JAA-F11 stained approximately 76% of all breast cancer specimens, which included cases of mucinous, medullary, invasive ductal and neuroendocrine carcinomas. The staining observed was irrespective of receptor status, whereas in normal breast tissue, staining was either absent or very weak/weak. In addition, all available matched lymph node metastasis stained, with greater intensity observed in 39% of cases. JAA-F11 IHC studies performed on human normal organ tissue arrays, showed staining that for the most part was not significantly different from staining obtained with isotype control antibody, or was observed in areas that would not be therapeutically accessible. Furthermore, in an additional IHC study, preliminary results suggest that JAA-F11 significantly stained other carcinomas including those of the colon, bladder, ovary and prostate. In vitro studies show that the humanized JAA-F11 (hJAA-F11) has similar chemical specificity and higher affinity towards the TF-Ag. Imaging studies were performed in a BALB/c mouse breast cancer model with the hJAA-F11 to determine biological reactivity and to predict the feasibility of theranostic imaging prior to therapy. After ∼10 days of tumor growth, mice pretreated with cold iodine water and rabbit IgG to inhibit binding to Fc receptors, were given tail vein injections of hJAA-F11 conjugated with [124]-I. Clear tumor images were obtained up to 144 hours post injection. Biodistribution analysis has provided further results indicating increased%ID/g (7.0±3.9%) in tumor tissue as compared to healthy tissues (brain%ID/g to be 0.21±.09, stomach 0.80±0.19%, and bone 0.90±2.4%). Results support that the hJAA-F11 antibody can be used in a multi-step theranostic approach, with analysis of tumor binding in IHC, followed by imaging to determine in vivo tumor targeting prior to direct immunotherapy or antibody drug conjugate therapy with hJAA-F11. Citation Format: Loukia Karacosta, Holly Johnson, Julia Abdullah, Taylor Chrisikos, Rachel Ludwig, Bradley Turner, Swetha Tati, Diala Ghazal, Munnawar Sajjad, Stephen Koury, Susan Morey, Julie Adams, Kate Rittenhouse-Olson. Immunohistochemistry and radioimaging with hJAA-11 antibody to the Thomsen-Friedenreich antigen: Potential theranostic application for breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 576.