Table 3.

Summary of key emerging targets in MM immunotherapy

Target	Rationale for Inclusion and Potential Impact	Known Limitations	Safety Profile
CD70	Homogeneous and specific expression in MM cells, plays a significant role in immune evasion and plasma cell proliferation	Shedding of its receptor (CD27) may reduce efficacy; off-tumor expression on activated immune cells poses a risk	No shedding reported for CD70 itself, though CD27 shedding has been observed; strong preclinical and clinical safety demonstrated in antibody-based therapies
CCR1	Overexpression in MM correlates with poor prognosis and enhanced dissemination; disrupting CCR1 signaling could reduce metastases and tumor progression	Exhibits high ligand promiscuity that may increase risk of resistance mechanisms. Expression is noted in some inflammatory conditions	No soluble form detected; preclinical safety data suggest selective targeting may avoid significant immune suppression or adverse effects
ITGB7	Central role in CAM-DR and immune evasion, promoting tumor adhesion to bone marrow stroma; disrupting ITGB7 interactions could help overcome resistance mechanisms	Limited clinical evidence in MM; most data derive from solid tumors or inflammatory conditions. Off-tumor expression on lymphocytes poses potential risks	Favorable safety profile reported from anti-ITGB7 agents in inflammatory diseases; no significant adverse effects noted in MM-specific studies
LILRB4	Implicated in T-cell suppression, immune evasion, and MM cell proliferation; promising preclinical data with mAbs and CAR T	Potential off-target effects due to expression in myeloid cells	Soluble form detected; acute myocarditis reported in one case with an anti-LILRB4 mAb in a non-MM setting; other preclinical and clinical studies reported a safety profile, supporting selective targeting in MM
SEMA4A	High expression in MM cells with a critical role in TME modulation, and immune suppression; strong candidate for ADC and CAR T-cell therapies	Risk of antigen downregulation and off-tumor expression in activated immune cells	Low levels of soluble form in MM patients suggest minimal therapeutic interference; preclinical studies indicate low off-target toxicity