Iberdomide (CC-220) Has Synergistic Anti-Tumor and Immunostimulatory Activity Against [MM] [with Bort and Dexa], or [Dara] in Vitro, 2018, Amatangelo+
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ryanc97
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In combination with daratumumab, iberdomide also had synergistic anti-MM activity in Complement-Dependent Cytotoxicity (CDC) assays. In co-culture systems using myeloma and immune cells, iberdomide significantly increased the antibody-dependent cellular cytotoxic activity of daratumumab.
While iberdomide treatment of MM cell lines resulted in increased CD38 surface expression, combinations were more effective when peripheral blood mononuclear cells (PBMCs) were pretreated, suggesting that iberdomide immunomodulatory activity is a significant contributor to the synergy observed.
Interestingly, pretreatment of PBMCs with daratumumab resulted in reduced efficacy of the combination. We observed that the treatment of PBMCs with daratumumab resulted in killing of natural killer (NK) cells in the PBMC culture. In contrast, treatment of PBMCs with iberdomide resulted in proliferation of NK cells, possibly helping to rescue the antagonistic effect of daratumumab on NK cell-mediated antibody‐dependent cellular cytotoxicity.
@Jaybee00
While iberdomide treatment of MM cell lines resulted in increased CD38 surface expression, combinations were more effective when peripheral blood mononuclear cells (PBMCs) were pretreated, suggesting that iberdomide immunomodulatory activity is a significant contributor to the synergy observed.
Interestingly, pretreatment of PBMCs with daratumumab resulted in reduced efficacy of the combination. We observed that the treatment of PBMCs with daratumumab resulted in killing of natural killer (NK) cells in the PBMC culture. In contrast, treatment of PBMCs with iberdomide resulted in proliferation of NK cells, possibly helping to rescue the antagonistic effect of daratumumab on NK cell-mediated antibody‐dependent cellular cytotoxicity.
@Jaybee00
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As far as I can tell, this is just a poster abstract. There's no more text behind a paywall.
ryanc97
Senior Member (Voting Rights)
Oh well. Anyway this looks very good for Iberdomide. Anktiva would be the holy grail but that is even less accessible...
Here’s a clear breakdown of how iberdomide (Iber) synergizes with daratumumab (Dara), based on the text and known mechanisms:
Iberdomide increases NK cell numbers and activity. NK cells are essential for daratumumab’s antibody-dependent cellular cytotoxicity (ADCC), which is one of the main ways it kills myeloma cells.
Daratumumab targets CD38 on myeloma cells. Iberdomide treatment increases CD38 expression, giving daratumumab more targets to bind → stronger cancer cell killing.
Daratumumab can kill cells via complement activation. In lab assays, Iber + Dara shows synergistic CDC, meaning cancer cells are more efficiently destroyed when both are present.
In mixed cultures of myeloma + immune cells, Iber enhances daratumumab-mediated ADCC, likely because:
Here’s a clear breakdown of how iberdomide (Iber) synergizes with daratumumab (Dara), based on the text and known mechanisms:
Iberdomide increases NK cell numbers and activity. NK cells are essential for daratumumab’s antibody-dependent cellular cytotoxicity (ADCC), which is one of the main ways it kills myeloma cells.
- If NK cells are already weakened (e.g., by pre-treating with daratumumab), the combo is less effective.
- So Iber “rescues” NK cell function, enhancing daratumumab’s killing.
Daratumumab targets CD38 on myeloma cells. Iberdomide treatment increases CD38 expression, giving daratumumab more targets to bind → stronger cancer cell killing.
Daratumumab can kill cells via complement activation. In lab assays, Iber + Dara shows synergistic CDC, meaning cancer cells are more efficiently destroyed when both are present.
In mixed cultures of myeloma + immune cells, Iber enhances daratumumab-mediated ADCC, likely because:
- It boosts NK cells
- It may modulate other immune cells to help attack myeloma