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Editorials
Since CD205 is broadly expressed in lymphoma cells and leukocytes, target antigen expression can be expected in most tumors and/or their microenvironment. Since MEN1309/OBT076 is designed with a cleavable linker, payload release does not necessarily depend on ADC endocytosis, thus facilitating bystander killing and off-tar- get toxicity.19 In the case of a broadly CD205 expressing tumor microenvironment, an adequate on-tumor efficacy could therefore be expected even without adequate on- target effects and ubiquitous antigen expression on lym- phoma cells (Figure 1). In this case, the novel ADC could rather act as a more sophisticated chemotherapy-delivery system and CD205 expression will not allow adequate patient selection. Even in this case, the drug might still prove useful in lymphoma therapy alone or in combina- tion. However, the integration of this novel agent into cur- rent treatment schedules might become more difficult.
In conclusion, the work by Gaudio et al.6 shows the activity of the anti-CD205 ADC MEN1309/OBT076 in preclinical CD205-positive lymphoma models that war- rants further clinical investigation. The development of a biomarker-drug combination allows for a targeted applica- tion of this drug in clinical trials. However, additional pre- clinical and translational work is required to shed light on the role of CD205 in lymphomagenesis. This is important for the rational development of this treatment as monotherapy, but also, and in particular, as a part of com- bination therapy. ADC continue to be important compo- nents of tumor therapy that could sometimes find a place between precision oncology and refined chemotherapy.
Funding
UK is supported by Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Stiftung Charité, Wilhelm Sander-Stiftung and the Berlin Institute of Health.
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12. Kato M, Khan S, Gonzalez N, et al. Hodgkin's lymphoma cell lines express a fusion protein encoded by intergenically spliced mRNA for the multilectin receptor DEC-205 (CD205) and a novel C-type lectin receptor DCL-1. J Biol Chem. 2003;278(36):34035-34041.
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DTR is a participant in the Berlin Institute of Health ‐ Charité Clinical Scientist Program funded by the Charité ‐ Universitätsmedizin Berlin and the Berlin Institute of Health.
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Acknowledgments
haematologica | 2020; 105(11)