Research

Milatuzumab

Background

Milatuzumab is a humanized monoclonal antibody targeting tumors that express the CD74 antigen, which is present on a variety of hematological tumors and even on some solid cancers, with restricted expression by normal tissues. It has received orphan drug designation from the Food and Drug Administration for the treatment of patients with multiple myeloma or CLL. Milatuzumab is the first anti-CD74 antibody that has entered into human testing and we have completed initial Phase I studies in patients with relapsed multiple myeloma, NHL or CLL.

The anti-CD74 antibody is also being studied subcutaneously in a Phase 1b study in patients with active SLE. The SLE study is supported by a three-year research grant from the Department of Defense with a potential funding of $1.6 million.

Our interest in pursuing milatuzumab in immune diseases is driven by the observations that implicated CD74 in antigen presentation—particularly by dendritic and other immune cells—and as a survival factor for rapidly proliferating malignant cells. Recent findings have determined that CD74 is a receptor for the pro-inflammatory chemokine, macrophage migration-inhibitory factor, and that binding of the factor to CD74 initiates a signaling cascade resulting in proliferation and survival of normal and malignant B cells, such as in CLL. Migration-inhibitory factor is widely expressed by immune cells, particularly macrophages, and is known to play a role in autoimmune disease. Thus, we believe that milatuzumab, by blocking the function of CD74, could be useful in the management of immune diseases either alone or in combination with other agents—including other B-cell antibodies such as epratuzumab and veltuzumab.

Clinical Studies

Lupus (SLE)

This is a Phase Ib study of milatuzumab administered subcutaneously in patients with active SLE funded by a grant from the Department of Defense.

References

  • Kaufman JL, Niesvizky R, Stadtmauer EA, Chanan-Khan A, Siegel D, Horne H, Wegener WA, Goldenberg DM. Phase I, multicentre, dose-escalation trial of monotherapy with milatuzumab (humanized anti-CD74 monoclonal antibody) in relapsed or refractory multiple myeloma. Br J Haematol, 163(4): 478-486, 2013.
  • Chen X, Chang CH, Stein R, Cardillo TM, Gold DV, Goldenberg DM. Prevention of acute graft-versus-host disease in a xenogeneic SCID mouse model by the humanized anti-CD74 antagonistic antibody milatuzumab. Biol Blood Marrow Transplant. 19(1):28-39, Jan 2013.
  • Frölich D, Blabetafeld D, Reiter K, Giesecke C, Daridon C, Mei HE, Burmester GR, Goldenberg DM, Salama A, Dörner T. The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression. Arthritis Res Ther. 14(2):R54, 2012.