ICIs such as monoclonal antibodies work by blocking the effects of inhibitory pathways and allow T cell activation. ICIs targeting CTLA4, PD-1, PD-L1, and LAG3 have been approved by the US FDA since 2011 (Table ), totaling eleven compounds, four of which were approved in the past 2 years. Anti-CTLA4, anti-PD-1, anti-PD-L1, and anti-LAG3 agents are utilized in the treatment of multiple solid and hematologic malignancies; however, one of their biggest caveats is that their effectiveness is restricted to only a specific subset of patients. The newest approved category, anti-LAG3 agents, received their first US FDA approval in March 2022. Opdualag, a fixed-dose combination of the LAG3 blocking antibody relatlimab and the PD-L1 inhibitor antibody nivolumab, has been approved for the treatment of unresectable or metastatic melanoma. Stimulating ICs hold great therapeutic promise -urelumab and utomilumab (PF-05082566) are two anti-CD137 antibodies under development that appear promising in renal cell carcinoma and colon cancer among many others because they can stimulate cytotoxic T cells and enhance the production of interferon gamma (IFN-γ), which is crucial for anti-cancer effects. CD38 plays a role in suppressing immune responses mediated by IFNγ and is expressed on M1 macrophages, as well as in immune responses involving neutrophils and T cells. Daratumumab (Darzalex, Janssen Biotech Inc.), an anti-CD38 IgG1 antibody specific to humans, has received US FDA approval 85 for use either on its own or in combination therapies to treat relapsed or refractory multiple myeloma and is effective at inducing both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity against multiple myeloma cells.