Anti-CD22 monoclonal antibody

B cells in fish are proven to be endocytic and have a great contribution to innate immunity like phagocytosis. In this study, the endocytic capacity and the corresponding internalization pathways of IgM(+) B cells in Japanese flounder (Paralichthys olivaceus) were investigated. The results showed that IgM(+) B cells in peripheral blood leukocytes (PBL) and splenic leukocytes (SL) exhibited different abilities to ingest 0.5 mu m and 1 pm latex beads through macropinocytosis-dependent endocytic pathway. Japanese flounder CD22 (PoCD22) co-stimulatory signals were identified to be essential for the innate immune responses in B cells. Most of IgM+ B cells and some IgM(-) cells were demonstrated to be PoCD22 positive. When PoCD22 was blocked by antibody, the endocytic activities and reactive oxygen species (ROS) activities of SL IgM(+) B cells were significantly increased, while the endocytic and ROS activities of PBL IgM(+) B cells were significant decreased. These results collectively suggest that Japanese flounder IgM(+) B cells are able to employ macropinocytosis-dependent endocytic pathway, which is under the regulation of CD22.

Purpose: To evaluate the safety, preliminary efficacy, and pharmacokinetics of inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, in combination with the immuno-chemotherapeutic regimen, rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). Experimental Design: In part 1 (n = 16), patients received inotuzumab ozogamicin plus R-CVP on a 21-day cycle with escalating doses of cyclophosphamide first then inotuzumab ozogamicin. Part 2 (n = 10) confirmed the safety and tolerability of the maximum tolerated dose (MTD), which required a dose-limiting toxicity rate of <33% in cycle 1 and <33% of patients discontinuing before cycle 3 due to treatment-related adverse events (AEs). Part 3 (n = 22) evaluated the preliminary efficacy of inotuzumab ozogamicin plus R-CVP. Results: The MTD was determined to be standard-dose R-CVP plus inotuzumab ozogamicin 0.8 mg/m(2). The most common treatment-related grade = 3 AEs in the MTD cohort (n = 38) were hematologic: neutropenia (74%), thrombocytopenia (50%), lymphopenia (42%), and leukopenia (47%). Among the 48 patients treated in the study, 13 discontinued due to AEs, most commonly thrombocytopenia (n = 10). Overall, 13 patients died, including one death due to treatment-related pneumonia secondary to neutropenia. Among patients receiving the MTD (n = 38), the overall response rate (ORR) was 84% (n = 32), including 24% (n = 9) with complete response; the ORR was 100% for patients with indolent lymphoma (n = 27) and 57% for those with aggressive histology lymphoma (n = 21). Conclusions: Inotuzumab ozogamicin at 0.8 mg/m(2) plus full dose R-CVP was associated with manageable toxicities and demonstrated a high rate of response in patients with relapsed/refractory CD22+ B-cell NHL. The study is registered at ClinicalTrials. gov (NCT01055496). (C) 2016 AACR.