| ICI . | CAR-T cells . | BiTEs . | |
|---|---|---|---|
| Structure | Monoclonal antibody targeting immune checkpoint inhibitor proteins [1] | T cells genetically engineered to present a TAA-targeting TCR [1, 6] | Recombinant antibody with two scFv regions; one targeting a TAA and one targeting CD3, a part of the TCR complex in T cells [1] |
| Effector cell | Endogenous T cells | Engineered T cells | Endogenous T cells |
| MAO | ICIs block receptor-ligand interactions to inhibit negative regulators of T cells, thereby promoting T cell-mediated destruction of tumor cells | CAR-T are T cells with engineered TCRs that have been designed to recognize TAAs, promoting T cell-mediated destruction of tumor cells | BiTEs simultaneous target the TCR complex on T cells and antigens on tumor cells to promote T cell-mediated destruction of tumor cells (independently of MHC restriction and TCR specificity) |
| Personalized | No | Yesa [6] | No |
| Production | Hybridoma technology to produce monoclonal antibodies [1] | Genetic engineering of (patient’sa) T cells in vitro [1, 6] | Protein engineering of antibodies from mammalian cells lines [1] |
| Availability | Off the shelf [3] | Delayed ≈ weeks | Off the shelf [8] |
| Half-life | Medium ≈ days | Long ≈ weeks-months [6, 8] | Short ≈ hours |
| Lymphodepletion prior to therapy | No | Routine [6, 8] | No |
| Administration | Repeat dosing [3, 9] | Single infusion [6] | Repeat dosing [7] |
| FDA/EMA approvals | Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Avelumab, Cemiplimab, Dostarlimab, Ipilimumab, Relatlimab [8–10] | Idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, tisagenlecleucel, brexucabtagene autoleucel, axicabtagene ciloleucel [11] | Blinatumomab [7] |
| Indications | Mostly solid tumors, some hematological malignancies [1, 9] | Hematological malignancies approvals only [1] | Hematological malignancies approvals only [1] |
| Advantages | Durable responses, can be curative even in metastatic disease, generally well tolerated compared with chemotherapy, broad-spectrum activity [1] | Works independently of MHC expression, and endogenous TCRs, therapy be tailored to patient’s tumor [1, 6] | Works independently of MHC and TCR expression, easy production, promising results in solid tumors [1, 8, 12] |
| Disadvantages | Only effective in a small proportion of patients (checkpoint-, MHC-, and TCR-expression dependent), ineffective in cold tumors, autoimmune toxicities [1, 9] | Long, complex, and expensive production, remained effect and toxicity after tumor clearance (due to long half-life), proving ineffective for solid tumors, antigen dependent, requires lymphodepletion, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6, 8, 13] | Short half-life requiring continuous infusion, antigen dependent, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6] |
| ICI . | CAR-T cells . | BiTEs . | |
|---|---|---|---|
| Structure | Monoclonal antibody targeting immune checkpoint inhibitor proteins [1] | T cells genetically engineered to present a TAA-targeting TCR [1, 6] | Recombinant antibody with two scFv regions; one targeting a TAA and one targeting CD3, a part of the TCR complex in T cells [1] |
| Effector cell | Endogenous T cells | Engineered T cells | Endogenous T cells |
| MAO | ICIs block receptor-ligand interactions to inhibit negative regulators of T cells, thereby promoting T cell-mediated destruction of tumor cells | CAR-T are T cells with engineered TCRs that have been designed to recognize TAAs, promoting T cell-mediated destruction of tumor cells | BiTEs simultaneous target the TCR complex on T cells and antigens on tumor cells to promote T cell-mediated destruction of tumor cells (independently of MHC restriction and TCR specificity) |
| Personalized | No | Yesa [6] | No |
| Production | Hybridoma technology to produce monoclonal antibodies [1] | Genetic engineering of (patient’sa) T cells in vitro [1, 6] | Protein engineering of antibodies from mammalian cells lines [1] |
| Availability | Off the shelf [3] | Delayed ≈ weeks | Off the shelf [8] |
| Half-life | Medium ≈ days | Long ≈ weeks-months [6, 8] | Short ≈ hours |
| Lymphodepletion prior to therapy | No | Routine [6, 8] | No |
| Administration | Repeat dosing [3, 9] | Single infusion [6] | Repeat dosing [7] |
| FDA/EMA approvals | Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Avelumab, Cemiplimab, Dostarlimab, Ipilimumab, Relatlimab [8–10] | Idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, tisagenlecleucel, brexucabtagene autoleucel, axicabtagene ciloleucel [11] | Blinatumomab [7] |
| Indications | Mostly solid tumors, some hematological malignancies [1, 9] | Hematological malignancies approvals only [1] | Hematological malignancies approvals only [1] |
| Advantages | Durable responses, can be curative even in metastatic disease, generally well tolerated compared with chemotherapy, broad-spectrum activity [1] | Works independently of MHC expression, and endogenous TCRs, therapy be tailored to patient’s tumor [1, 6] | Works independently of MHC and TCR expression, easy production, promising results in solid tumors [1, 8, 12] |
| Disadvantages | Only effective in a small proportion of patients (checkpoint-, MHC-, and TCR-expression dependent), ineffective in cold tumors, autoimmune toxicities [1, 9] | Long, complex, and expensive production, remained effect and toxicity after tumor clearance (due to long half-life), proving ineffective for solid tumors, antigen dependent, requires lymphodepletion, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6, 8, 13] | Short half-life requiring continuous infusion, antigen dependent, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6] |
aFor autologous CAR-T cells.
MAO, mechanism of action.
| ICI . | CAR-T cells . | BiTEs . | |
|---|---|---|---|
| Structure | Monoclonal antibody targeting immune checkpoint inhibitor proteins [1] | T cells genetically engineered to present a TAA-targeting TCR [1, 6] | Recombinant antibody with two scFv regions; one targeting a TAA and one targeting CD3, a part of the TCR complex in T cells [1] |
| Effector cell | Endogenous T cells | Engineered T cells | Endogenous T cells |
| MAO | ICIs block receptor-ligand interactions to inhibit negative regulators of T cells, thereby promoting T cell-mediated destruction of tumor cells | CAR-T are T cells with engineered TCRs that have been designed to recognize TAAs, promoting T cell-mediated destruction of tumor cells | BiTEs simultaneous target the TCR complex on T cells and antigens on tumor cells to promote T cell-mediated destruction of tumor cells (independently of MHC restriction and TCR specificity) |
| Personalized | No | Yesa [6] | No |
| Production | Hybridoma technology to produce monoclonal antibodies [1] | Genetic engineering of (patient’sa) T cells in vitro [1, 6] | Protein engineering of antibodies from mammalian cells lines [1] |
| Availability | Off the shelf [3] | Delayed ≈ weeks | Off the shelf [8] |
| Half-life | Medium ≈ days | Long ≈ weeks-months [6, 8] | Short ≈ hours |
| Lymphodepletion prior to therapy | No | Routine [6, 8] | No |
| Administration | Repeat dosing [3, 9] | Single infusion [6] | Repeat dosing [7] |
| FDA/EMA approvals | Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Avelumab, Cemiplimab, Dostarlimab, Ipilimumab, Relatlimab [8–10] | Idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, tisagenlecleucel, brexucabtagene autoleucel, axicabtagene ciloleucel [11] | Blinatumomab [7] |
| Indications | Mostly solid tumors, some hematological malignancies [1, 9] | Hematological malignancies approvals only [1] | Hematological malignancies approvals only [1] |
| Advantages | Durable responses, can be curative even in metastatic disease, generally well tolerated compared with chemotherapy, broad-spectrum activity [1] | Works independently of MHC expression, and endogenous TCRs, therapy be tailored to patient’s tumor [1, 6] | Works independently of MHC and TCR expression, easy production, promising results in solid tumors [1, 8, 12] |
| Disadvantages | Only effective in a small proportion of patients (checkpoint-, MHC-, and TCR-expression dependent), ineffective in cold tumors, autoimmune toxicities [1, 9] | Long, complex, and expensive production, remained effect and toxicity after tumor clearance (due to long half-life), proving ineffective for solid tumors, antigen dependent, requires lymphodepletion, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6, 8, 13] | Short half-life requiring continuous infusion, antigen dependent, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6] |
| ICI . | CAR-T cells . | BiTEs . | |
|---|---|---|---|
| Structure | Monoclonal antibody targeting immune checkpoint inhibitor proteins [1] | T cells genetically engineered to present a TAA-targeting TCR [1, 6] | Recombinant antibody with two scFv regions; one targeting a TAA and one targeting CD3, a part of the TCR complex in T cells [1] |
| Effector cell | Endogenous T cells | Engineered T cells | Endogenous T cells |
| MAO | ICIs block receptor-ligand interactions to inhibit negative regulators of T cells, thereby promoting T cell-mediated destruction of tumor cells | CAR-T are T cells with engineered TCRs that have been designed to recognize TAAs, promoting T cell-mediated destruction of tumor cells | BiTEs simultaneous target the TCR complex on T cells and antigens on tumor cells to promote T cell-mediated destruction of tumor cells (independently of MHC restriction and TCR specificity) |
| Personalized | No | Yesa [6] | No |
| Production | Hybridoma technology to produce monoclonal antibodies [1] | Genetic engineering of (patient’sa) T cells in vitro [1, 6] | Protein engineering of antibodies from mammalian cells lines [1] |
| Availability | Off the shelf [3] | Delayed ≈ weeks | Off the shelf [8] |
| Half-life | Medium ≈ days | Long ≈ weeks-months [6, 8] | Short ≈ hours |
| Lymphodepletion prior to therapy | No | Routine [6, 8] | No |
| Administration | Repeat dosing [3, 9] | Single infusion [6] | Repeat dosing [7] |
| FDA/EMA approvals | Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Avelumab, Cemiplimab, Dostarlimab, Ipilimumab, Relatlimab [8–10] | Idecabtagene vicleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, tisagenlecleucel, brexucabtagene autoleucel, axicabtagene ciloleucel [11] | Blinatumomab [7] |
| Indications | Mostly solid tumors, some hematological malignancies [1, 9] | Hematological malignancies approvals only [1] | Hematological malignancies approvals only [1] |
| Advantages | Durable responses, can be curative even in metastatic disease, generally well tolerated compared with chemotherapy, broad-spectrum activity [1] | Works independently of MHC expression, and endogenous TCRs, therapy be tailored to patient’s tumor [1, 6] | Works independently of MHC and TCR expression, easy production, promising results in solid tumors [1, 8, 12] |
| Disadvantages | Only effective in a small proportion of patients (checkpoint-, MHC-, and TCR-expression dependent), ineffective in cold tumors, autoimmune toxicities [1, 9] | Long, complex, and expensive production, remained effect and toxicity after tumor clearance (due to long half-life), proving ineffective for solid tumors, antigen dependent, requires lymphodepletion, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6, 8, 13] | Short half-life requiring continuous infusion, antigen dependent, can lead to CRS or neurotoxicity, may have on-target off-tumor effects (due to antigen expression in healthy tissue) [1, 6] |
aFor autologous CAR-T cells.
MAO, mechanism of action.
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