The HB22.7 Anti-CD22 monoclonal antibody enhances bortezomib-mediated lymphomacidal activity in a sequence dependent manner.

Most non-Hodgkin's lymphomas (NHL) initially respond to chemotherapy, but relapse is common and treatment is often limited by chemotherapy-related toxicity. Bortezomib, is a highly selective proteasome inhibitor with anti-NHL activity; it is currently FDA approved for second-line treatment of mantle cell lymphoma (MCL). Bortezomib exerts its activity in part through the generation of reactive oxygen species (ROS) and also by the induction of apoptosis.

Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts.

CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand.

Treatment of non-Hodgkin's lymphoma xenografts with the HB22.7 anti-CD22 monoclonal antibody and phosphatase inhibitors improves efficacy.

Purpose: To examine the role of phosphatase inhibition on anti-CD22, HB22.7-mediated lymphomacidal effects.

Experimental Design: CD22 is a cell-surface molecule expressed on most B cell lymphomas (NHL).

Phosphatase inhibition augments anti-CD22-mediated signaling and cytotoxicity in non-hodgkin's lymphoma cells.

CD22 is a cell-surface molecule found on most B-cell lymphomas (NHL). HB22.7 is an anti-CD22 antibody that blocks CD22 ligand binding, initiates signaling, and kills NHL cells.

Imaging and pharmacokinetics of (64)Cu-DOTA-HB22.7 administered by intravenous, intraperitoneal, or subcutaneous injection to mice bearing non-Hodgkin's lymphoma xenografts.

Purpose: The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of (64)Cu-DOTA-HB22.7 when administered to xenograft-bearing mice intravenously (IV), intraperitoneally (IP), and subcutaneously (SQ).

Procedures: Mice bearing human non-Hodgkin's lymphoma (NHL) xenografts were injected IV, IP, or SQ with (64)Cu-DOTA-HB22.

Increased cyclooxygenase-2 (COX-2): a potential role in the pathogenesis of lymphoma.

B cell lymphomas are a diverse group of clinicopathologic diseases with an increasing incidence. As with other malignancies, the accumulation of genetic abnormalities are required for malignant transformation of human lymphocytes. Cyclooxygenase-2 (COX-2) is a key biosynthetic enzyme in prostaglandin synthesis and has been implicated in the pathogenesis of numerous malignancies including colon, breast, and lung cancer.

Phosphorylation abnormalities: NZB mice exhibit a B-cell signalling defect.

NZB mice demonstrate common and consistent abnormalities in B-cell activation and signalling. One of the hallmark characteristics of lupus disease is the prevalent hypergammaglobulinaemia, composed primarily of anti-nuclear antibodies. In addition to the hyperproliferation seen in mice exhibiting disease, the B cells also demonstrate a marked degree of hyperactivity in response to B-cell receptor occupancy.