Targeting Multiple Myeloma with SGN-CD352A: A Promising Anti-CD352 ADC Approach

Multiple myeloma, a malignant disease affecting plasma cells, continues to be a challenge despite medical progress, highlighting the necessity for innovative treatment approaches. The research introduces SGN-CD352A, an antibody-drug conjugate (ADC) designed to target CD352, a protein implicated in the regulation of NK cell activity and present in various B-cell malignancies, including multiple myeloma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. The study found that 87% of patient samples exhibited CD352 on malignant plasma cells.

Researchers developed monoclonal antibodies (mAbs) against human CD352, selecting the most effective for its binding affinity, internalization capacity, and cytotoxic potency. SGN-CD352A is an engineered humanized mAb linked to a pyrrolobenzodiazepine (PBD) dimer, a cytotoxic agent that damages DNA. Once bound to CD352 on MM cells, the conjugate is rapidly internalized and travels to lysosomes, where PBD dimers induce a DNA damage response, leading to apoptosis within 48 hours.

The ADC showed significant cytotoxicity against multiple myeloma and lymphoma cell lines, even at low CD352 expression levels, without affecting resting T lymphocytes or causing substantial harm to B lymphocytes. In mouse models with disseminated MM cell lines, SGN-CD352A demonstrated potent in vivo antitumor effects, resulting in complete remissions and tumor delays at clinically relevant doses. The study emphasizes that the therapeutic effect is contingent upon the specific binding of the PBD dimer to CD352.

The findings validate CD352 as a novel target for MM treatment and suggest that SGN-CD352A holds promise as a new therapeutic agent for this disease. The research was presented at the 107th Annual Meeting of the American Association for Cancer Research and published in Cancer Research.