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Sökning: WFRF:(Kovacek Mathilda)

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1.
  • Roghanian, Ali, et al. (författare)
  • Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.
  • 2015
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 27:4, s. 473-488
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
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2.
  • Veitonmäki, Niina, et al. (författare)
  • A human icam-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo.
  • 2013
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 23:4, s. 502-515
  • Tidskriftsartikel (refereegranskat)abstract
    • We isolated a tumor B-cell-targeting antibody, BI-505, from a highly diversified human phage-antibody library, using a pioneering "function-first" approach involving screening for (1) specificity for a tumor B cell surface receptor, (2) induction of tumor programmed cell death, and (3) enhanced in vivo antitumor activity compared to currently used treatments. BI-505 bound to intercellular adhesion molecule-1, identifying a previously unrecognized role for this receptor as a therapeutic target in cancer. The BI-505 epitope was strongly expressed on the surface of multiple myeloma cells from both newly diagnosed and relapsed patients. BI-505 had potent macrophage-dependent antimyeloma activity and conferred enhanced survival compared to currently used treatments in advanced experimental models of multiple myeloma.
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