Table 2.
Schematic overview of mechanisms of resistance and potential strategies to overcome this.
| Mechanisms of Resistance | Affect | Potential Strategies to Overcome Resistance |
|---|---|---|
| Decreased CD38 expression | CDC, ADCC, ADCP | ATRA, panobinostat (only CDC), IMiDs |
| Complement inhibitory proteins (CD55, CD59) | CDC | ATRA |
| CAM-IR | ADCC, direct effects (PCD) | YM-155 |
| FcγR polymorphisms | ADCC, ADCP | - |
| CD47 expression | ADCP | Low-dose cyclophosphamide, CD47-SIRPα-blocking antibodies |
| NK cell reduction | ADCC | IMiDs |
| Different immune cell composition *, upregulation of immune checkpoint LAG3/TIGIT | T-cell-mediated killing | Combining with immune-checkpoint inhibitors |
| Soluble CD38, neutralizing antibodies | All mechanisms of action | Fully human antibodies |
* E.g., decreased numbers of activated T-cells and effector memory/central memory T-cells; lower absolute numbers of CD38+ Tregs before treatment. Abbreviations: CDC: complement-dependent cytotoxicity; ADCC: antibody-dependent cell-mediated cytotoxicity; ADCP: antibody-dependent cell-mediated phagocytosis; ATRA: all-trans retinoic acid; IMiDs: immunemodulatory drugs; CAM-IR: cell adhesion-mediated immune resistance; PCD: programmed cell death; FcγR: Fc-gamma receptor, IMiDs: immunomodulatory drugs; KIR: killer-cell immunoglobulin-like receptor; LAG3: lymphocyte-activation gene 3; TIGIT: T cell immunoreceptor with Ig and ITIM domains.