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-- Two Preclinical Studies Presented at the 54th Annual Meeting of the American Society of Hematology (ASH) -- -- Preclinical Study of Milatuzumab in Graft-Versus-Host Disease also Presented --
ATLANTA, Dec. 12, 2012 (GLOBE NEWSWIRE) --
Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today announced that two new classes of bispecific antibodies were created as the DOCK-AND-LOCK™ (DNL™) complexes using the Company's patented platform technology that enables site-specific conjugation of two self-assembling modules. These bispecific antibodies exhibited potent cell killing activity against lymphoma cell lines in vitro.
Antibodies are large Y-shaped proteins, comprising two identical target-binding arms, each referred to as the fragment, antigen binding (Fab) region, and a tail known as the fragment crystalline (Fc) region. When an antibody is bound to its target via the two Fab arms, interaction of the Fc region with the Fc receptors on blood cells may result in eliminating the tagged target. Other mechanisms of target killing can be achieved with engineered antibodies of various designs, often with enhanced potency compared to the parental antibodies.
Redirecting T cells with a Novel Class of DNL TM Complexes
One advance that the Company presented at the 2012 ASH Annual Meeting is a novel T-cell redirecting agent made as a DNL
TM complex by tethering a pair of Fabs that recognize CD19 on B cells to a single-chain variable fragment (scFv) that binds to CD3 on T cells. Referred to as (19)-3s, the prototype potently directs T cells to destroy CD19-expressing B cells by linking them together. Specifically, (19)-3s was shown to bind to T cells and non-Hodgkin lymphoma (NHL) cells simultaneously, and induce T-cell-mediated killing of NHL cells at less than 1 picomolar (pM) concentrations in an ex vivo setting, with maximal activity at 10 pM.
"We expect (19)-3s to have an elimination rate longer than that of blinatumomab, which is made of two scFvs to co-ligate CD19 and CD3," commented Cynthia L. Sullivan, President and Chief Executive Officer. "We are currently evaluating the in vivo activity of (19)-3s, as a prototype, to determine if this novel bsAb offers additional advantages," Ms. Sullivan added. "The slower clearance and the fact that (19)-3s has two binding arms might allow for less frequent dosing, and possibly subcutaneous administration. The modular nature of DNL will allow the rapid production of a large number of related conjugates for redirected T-cell killing of various malignancies, without the need for additional recombinant engineering and protein production," concluded Ms. Sullivan.