Tumor‐targeted immune complex formation: Effects on myeloid cell activation and tumor‐directed immune cell migration

作者: Bart-Jan Kroesen , Pamela M.J. McLaughlin , Petra H.L. Schuilenga-Hut , Susan C. Jacobs , Grietje Molema

DOI: 10.1002/IJC.10245

关键词:

摘要: The effectiveness of cellular immunotherapy solid tumors is often hampered by the lack specific infiltration immune effector cells into tumor mass. Therefore, we studied potential antigen-specific antibodies to elicit tumor-specific myeloid cell activation, induce or enhance cells. To this end, developed an in vitro model system using human line MonoMac-6. Incubation IFN-gamma-primed MonoMac-6 with serum-opsonized zymosan EGP-2-directed, mouse IgG2a-opsonized, EGP-2-positive resulted production ROS and TNF-alpha induced E-selectin ICAM-1 expression on HUVECs. FcR-mediated activation was strictly dependent IFN-gamma. In addition, no observed presence serum antibody subclasses other than IgG2a, suggesting crucial involvement CD64 (FcgammaR1) effects observed. However, serum-inhibited completely restored employing a 2-step targeting approach which opsonization anti-EGP-2 followed incubation antimouse Ig antibodies. Moreover, approach, not only anti-EGP-2-directed IgG2a but also IgG1 effectively activation. conclusion, describe method efficient based sequential use Targeted may provide means aid induction tumor-directed response as such, described here could be clinical significance.

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