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. 2021 Jan 27;10:606368. doi: 10.3389/fonc.2020.606368

Figure 1.

Figure 1

Schematic overview of immune therapies in MM. 1. Strategies for the direct targeting of MM cell antigens includes: (a) moAbs: anti-CD38 and -SLAMF7 antibodies induce ADCC, CDC, ADCP, and direct cytotoxic effect on MM cells; (b) ADCs: conjugation of moAbs and cytotoxic compounds provides direct and selective tumor killing; (c) BiTEs: dual interaction with surface antigen of tumor cells and the TCR complex enables T cell activation and tumor lysis of MM cells. 2. Restoration of host immune surveillance and decrease of immune suppression can be achieved by the blockade of immune-checkpoint, such as PD-1/PD-L1 axis, that are responsible for inactivation and loss of proliferative capacity of T cells; or by the use of genetically redirected T cells including CAR-T and TCR-T cells. CAR-T cells mediate MHC-unrestricted tumor cell killing via recognition of tumor antigen. TCR-T cells mediate MHC-restricted tumor cell killing by recognizing the intracellular antigen fragment presented by MHC molecules. 3. Peptide- or DC-based vaccination represents an additional strategy to increase a MM specific anti-tumor immunity. Peptide vaccines binds to restricted MHC molecule in APCs and after intracellular processing, peptide/MHC complex is transported to the cell surface for antigen presentation and activation of T cells. In DC-based vaccines, DCs are generated to present tumor associated antigens to T cells. 4. Anti-MM agents such as IMiDs and PIs may affect the immune compartment composition and increase anti-MM immune response. IMiDs increase and stimulate T, NK, and NKT cells, along with a decrease of immunosuppressive Treg cells. Novel reports also show the ability of anti-MM agents, such as bortezomib to induce immunogenic cell death (ICD) and stimulate an immune response against MM cells. Specifically, dying tumor cells expose specific damage associated molecular patterns (DAMPs) that induce the functional maturation of DCs, and the efficient presentation of tumor antigens to the T cells. ADCC, Antibody-dependent cellular cytotoxicity; ADCP, Antibody-dependent cellular phagocytosis; CDC, Complement-dependent cytotoxicity; ADC, Antibody drug conjugate; BiTE, Bi-specific T cell engager; CAR, Chimeric antigen receptor; TCR, T cell receptor; APC, Antigen presenting cell; NK, Natural Killer; Treg, regulatory T cells; DC, dendritic cell; CRT, Calreticulin.