Table 3 Antigen expression, normal tissue distribution, constructions, and potential critical aspects
From: Patient selection for CAR T or BiTE therapy in multiple myeloma: Which treatment for each patient?
Target | Expression by myeloma cells | Expression by normal hematopoietic cells | Expression on other tissues | Clinical development of treatment options | Critical issues during development |
|---|---|---|---|---|---|
CD38 | Increased and uniform expression. Downregulated after Mab treatment | Myeloid and lymphoid cells, progenitor cells, NK and T cells, neutrophils and dendritic cells | Epithelial cells (prostate), pancreatic islet cells, pulmonary cells, Purkinje neurons (cerebellum) | Mabs (FDA, EMA approved) CAR T (clinical trials) | Mab treatment well tolerated Expression on normal tissues can hamper the development of more potent therapies |
BCMA | 60–100% | Plasmocytes and plasmoblasts | Absent (controversial expression on basal ganglia (brain) | Antibody–drug conjugate (FDA, EMA approved) CAR T (FDA, EMA approved) Bispecific antibodies (BITE and IgG format) | Duration of response for some of the CAR T constructs Potential neurotoxicity |
SLAMF7/CS1 | Increased and uniform expression | NK, T and B cells, monocytes, macrophages, dendritic cells and plasmacytes | Absent | Mabs (FDA, EMA approved) CAR T (clinical trials) | Fratricide on NK cells |
FcRL5 | Expression on > 80% of patients | B cells and plasmocytes | Absent | Bispecific antibodies (BiTE format) | IV formulation |
GPRC5D | High expression in > 60% patients | B cells and plasma cells | Epithelial cells of skin and of filiform papillae (tongue) | Bispecific antibodies (IgG format) and CAR T, both in clinical trials | Skin and nail toxicity, dysgeusia |
CD138 | High expression | Plasmocytes | Epithelial cells of GI tract, hepatocytes | CAR T (clinical trials) | Currently in early development |
CD19 | Weak expression | B cell lineage cells | Absent | CAR T (clinical trials) | Weak expression on tumor cells |
CD56 | High expression in 80% of patients | NK and T cells, monocytes | Neural expression | CAR T (clinical trials) | Currently in early development |