Abstract
Abstract IGM-55.5 is an engineered monoclonal human recombinant IgM antibody that was derived from a natural monoclonal antibody 216 isolated at Stanford University from the splenocytes of a patient with Non-Hodgkin's lymphoma. HuMab 216 was previously used in a B-cell acute lymphoblastic leukemia phase I trial and was demonstrated to be well tolerated with significant decrease in peripheral blasts observed (Liedtke et al, Haematologica, 2012). IGM-55.5 has been engineered to be mono-reactive and recognizes a carbohydrate determinant as an epitope on normal human B cells as well as B-cell lymphoma and B-progenitor lymphoblasts. Here, we report new preclinical studies that describe the mechanism of action and potent activity of IGM-55.5. In-vitro analysis of IGM-55.5 was found to have high surface binding on a broad panel of B cell leukemia and lymphoma cells lines by flow cytometry. IGM-55.5 binding leads to the disruption of the plasma membrane and formation of large membrane pores resulting in cell lysis. This non-classical apoptosis occurs in the absence of complement fixation but in vitro cytotoxicity is increased in assays in the presence of human complement. Studies with aggressive disseminated tumor xenograft models (Namalwa, Granta, & Nalm-6) demonstrate that IGM-55.5 significantly prolongs survival and reduces circulating tumor cells. Peripheral blood samples from chronic lymphocytic leukemia patients demonstrated the potent activity of IGM-55 in eliminating B cell lymphoblasts in comparison with Rituxan when treated in-vitro. These data taken together highlight the potent activity of IGM-55.5 as therapeutic for advanced B cell malignancies, especially indicated for Rituxan resistant or refractory patients. Citation Format: Omar Duramad, Beatrice Wang, Fen Zheng, Lena Keyt, Claire Repellin, Lucia Beviglia, Neelima Bhat, Marcia Bieber, Nelson Teng, Bruce Keyt. IGM-55.5, a novel monoclonal human recombinant IgM antibody with potent activity against B cell leukemia and lymphoma. [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 645. doi:10.1158/1538-7445.AM2014-645
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