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Fc-engineered CD54 antibody MSH-TP15 for myeloma therapy
ies not only triggered phagocytosis with human macrophages but also significantly triggered ADCC by human NK cells in vitro this might suggest that although in the mouse model myeloid immune effector cells play a dominant role. In patients, together with macrophages also NK cells may constitute a powerful additional effec- tor cell population, which can be recruited for tumor cell killing. Nevertheless, in the subcutaneous model, cure of the mice was not achieved. This leaves room for further improvement and allows testing of combinations of our novel anti-ICAM-1 antibodies with various established anti-myeloma treatment regimen, including proteasome inhibitors, immunomodulatory drugs and chemothera- peutic substances. Systematic testing in our model sys- tem may allow the identification of optimal combination partners for potential clinical application.
Taken together, our data indicate that predominantly Fc-mediated effector functions account for the anti-myelo- ma activity of MSH-TP15 and that by Fc protein-engineer- ing a significant improvement of the antibody’s in vitro and in vivo activity was achieved. Particularly for myeloma ther- apy, where in the post-transplant setting NK cells are among the first immune cells to be present, targeting resid-
ual tumor cells in the patients BM with an Fc-eng. anti- ICAM-1 antibody like MSH-TP15 Fc-eng. might be a promising strategy to improve clinical outcome.
Disclosures
No conflicts of interest to disclose.
Contributions
KK, MC, CK, TR, AO, SK and AL performed the research; KK and MP wrote the manuscript; CK, FN, TR, TV and MG contributed to writing of the manuscript; MG and MP supervised the study
Acknowledgments
The authors would like to thank Kathrin Richter, Jan Brdon, Britta von Below and Anja Muskulus for excellent technical assistance.
Funding
This study was supported by a research grant from the Deutsche Krebshilfe e.V. (Mildred-Scheel-Professorship pro- gram) to MP and Else Kröner-Fresenius-Stiftung (2015_A166) to KK.
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