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Avon-by-the-Sea, NJ, United States

Govindan S.V.,Immunomedics, Inc. | Goldenberg D.M.,Center for Molecular Medicine and Immunology
Expert Opinion on Biological Therapy

Introduction: Antibodydrug conjugates (ADCs), as well as antibody conjugates of protein toxins (immunotoxins) and cytokines (immunocytokines), are showing clinical efficacy, with manageable toxicities, in cancer treatment. Areas covered: The utility of an ADC is governed by the antibody and the target, as well as by the druglinker component of the conjugate. The conjugation site, conjugating group, drug/antibody ratios and site-specific conjugation for product homogeneity are all aspects to consider in optimizing the ADC and enhancing its therapeutic window. Immunotoxin and immunocytokine construction by recombinant methods can be modulated to improve efficacy and reduce toxicity. The Dock-and-Lock (DNL) platform technology provides a flexible approach to assemble mono- or bispecific constructs carrying multiple toxin or cytokine molecules for targeted therapy. Expert opinion: Conjugation chemistry and recombinant technologies have had a significant impact on the therapeutic prospects of immunoconjugates, particularly in hematopoietic diseases. Continued concerted efforts from different scientific disciplines are needed, together with newer treatment paradigms, for greater progress in the more challenging therapy of solid tumors. © 2012 Informa UK, Ltd. Source

Wallace D.J.,University of California at Los Angeles | Goldenberg D.M.,Center for Molecular Medicine and Immunology | Goldenberg D.M.,Immunomedics, Inc.

Epratuzumab (EMab, UCB, Immunomedics) is a humanized monoclonal antibody targeting CD22 that is being studied in clinical trials for patients with a variety of rheumatic and hematologic conditions, including systemic lupus erythematosus (SLE). An overview of its mechanism of action is followed by a summary of completed lupus studies, and a preview of studies in progress. The agent clearly has anti-inflammatory activity and is a potentially useful agent in the management of autoimmune disorders. © The Author(s), 2013. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav. Source

Immunomedics, Inc. and Center For Molecular Medicine And Immunology | Date: 2012-08-06

Disclosed herein are methods and compositions comprising interferon- (IFN-) and anti-CD74 or anti-HLA-DR antibodies. In preferred embodiments, the IFN- increases the expression of CD74 and/or HLA-DR in target cells and increases the sensitivity of the cells to the cytotoxic effects of the anti-CD74 or anti-HLA-DR antibodies. The compositions and methods are of use to treat diseases involving CD74

Center For Molecular Medicine And Immunology and Immunomedics, Inc. | Date: 2011-03-11

The present invention concerns methods and compositions for inhibiting angiogenesis and/or tumor growth, survival and/or metastasis. In particular embodiments, the methods and compositions may concern ligands against placenta growth factor (PlGF), such as BP-1, BP-2, BP-3 or BP-4. Some methods may comprise administering one or more PlGF ligands, alone or in combination with one or more other agents, such as chemotherapeutic agents, other anti-angiogenic agents, immunotherapeutic agents or radioimmunotherapeutic agents to a subject. The PlGF ligands are effective to inhibit angiogenesis, tumor cell motility, tumor metastasis, tumor growth and/or tumor survival. In certain embodiments, PlGF ligands may be administered to subjects to ameliorate other angiogenesis related conditions, such as macular degeneration. In some embodiments, PlGF expression levels may be determined by any known method to select those patients most likely to respond to PlGF targeted therapies.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 191.14K | Year: 2011

DESCRIPTION (provided by applicant): Control of GVHD by milatuzumab in hu-SCID mice Dendritic cells (DCs) are the primary initiator of graft-versus-host disease (GVHD), a major and life- threatening complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Depletion of DCs has been demonstrated to be an effective approach for control of GVHD. We recently found that milatuzumab, a humanized anti-CD74 monoclonal antibody, can efficiently deplete myeloid DCs from human peripheral blood mononuclear cells, and potently suppress the proliferation of alloreactive T cells without impairing CMV-specific CD8+ T cells in allogeneic mixed leukocyte cultures, suggesting that milatuzumab may be developed as a novel mAb for prophylactic and/or therapeutic control of GVHD. In this proposed study, we will evaluate the efficacy of this novel mAb for its prophylactic efficacy against GVHD in a human-PBL-SCID mouse model. We will also investigate whether milatuzumab, while controlling GVHD, has any detrimental effect on the third-party immunity in this model, including anti-viral and graft-versus-leukemic functions, which will provide key safety information for clinical use of this mAb in patients undergoing allo-hematopoietic stem cell transplant. We believe that this STTR project, through the collaboration between Immunomedics, Inc., and the Center for Molecular Medicine and Immunology, could lead to the development of a novel class of monoclonal antibodies for better control of GVHD through depletion of CD74-expressing myeloid DCs. PUBLIC HEALTH RELEVANCE: Control of GVHD by milatuzumab in hu-SCID mice Graft-versus-host disease (GVHD) is a major life-threatening complication of allogeneic hematopoietic stem cell transplantation. Milatuzumab, a humanized anti-CD74 monoclonal antibody, can efficiently deplete dendritic cells from human peripheral mononuclear cells, suggesting its potential to prevent and/or treat GVHD. We will evaluate the preventive efficacy of milatuzumab on GVHD in a humanized mouse model, and while controlling GVHD, if it has any harmful effect on the host immunity against pathogens and leukemia, including anti-viral and graft-versus-leukemic functions. This preclinical study could provide valuable information to justify future clinical investigations.

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