Table 3 Clinical trials of CRISPR-based cancer therapy
Cancer Type | Treatment Approach | Patient Population | Description | Advantages | Disadvantages | Ref |
|---|---|---|---|---|---|---|
Metastatic melanoma | TCR/CAR-T therapy targeting NY-ESO-1 | Patients with NY-ESO-1 + tumors who failed prior therapy | T cells were edited to express NY-ESO-1 TCR/CAR, infused back into patients | Target specificity, long-term persistence | Possible off-target effects, limited efficacy in some patients | [160] |
Non-Hodgkin's Lymphoma | CD19-targeting CAR-T therapy | Patients with refractory/relapsed NHL | T cells were edited to express CD19 CAR, infused back into patients | High response rate, durable response in some patients | Cytokine release syndrome, neurotoxicity, potential for tumor antigen escape | [161] |
Bladder Cancer | PD-1 knockout via CRISPR/Cas9 | Patients with high-risk non-muscle-invasive bladder cancer | CRISPR-edited autologous T cells were infused into patients | Potential for enhanced anti-tumor immune response | Off-target effects, potential for immune-related adverse events | [162] |
Sarcoma | Targeted genome editing of PAX3-FOXO1 fusion gene | Patients with metastatic sarcoma expressing PAX3-FOXO1 | CRISPR/Cas9 was used to target the fusion gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [163] |
Solid Tumors | Adoptive transfer of TCR/CAR-T cells targeting neoantigens | Patients with advanced solid tumors | T cells were edited to express TCR/CAR targeting neoantigens unique to each patient's tumor, infused back into patients | Target specificity, potential for durable response | Heterogeneity of tumor neoantigens, potential for off-target effects | [164] |
Renal Cell Carcinoma | PD-1 knockout via CRISPR/Cas9 | Patients with advanced RCC who failed prior therapies | CRISPR-edited autologous T cells were infused into patients | Potential for enhanced anti-tumor immune response | Off-target effects, potential for immune-related adverse events | [165] |
Multiple Myeloma | BCMA-targeting CAR-T therapy | Patients with relapsed/refractory multiple myeloma | T cells were edited to express BCMA CAR, infused back into patients | High response rate, durable response in some patients | Cytokine release syndrome, neurotoxicity | [166] |
Glioblastoma | EGFRvIII-targeting CAR-T therapy | Patients with recurrent GBM expressing EGFRvIII | T cells were edited to express EGFRvIII CAR, infused back into patients | Target specificity, potential for durable response | Heterogeneity of tumor antigen expression, potential for off-target effects | [167] |
Esophageal Cancer | Targeted genome editing of MUC1 gene | Patients with MUC1 + esophageal squamous cell carcinoma | CRISPR/Cas9 was used to target the MUC1 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [168] |
Prostate Cancer | Targeted genome editing of androgen receptor gene | Patients with castration-resistant prostate cancer | CRISPR/Cas9 was used to target the androgen receptor gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [169] |
Acute Myeloid Leukemia | CD33-targeting CAR-T therapy | Patients with relapsed/refractory AML | T cells were edited to express CD33 CAR, infused back into patients | Target specificity, potential for durable response | Cytokine release syndrome, neurotoxicity | [170] |
Head and Neck Cancer | Targeted genome editing of HPV16 E6 gene | Patients with HPV16 + recurrent or metastatic head and neck cancer | CRISPR/Cas9 was used to target the HPV16 E6 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [171] |
Lung Cancer | Targeted genome editing of KRAS gene | Patients with advanced KRAS-mutant lung cancer | CRISPR/Cas9 was used to target the KRAS gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [172] |
Neuroblastoma | Targeted genome editing of ALK gene | Patients with ALK-mutant neuroblastoma | CRISPR/Cas9 was used to target the ALK gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [173] |
Acute Lymphoblastic Leukemia | CD19-targeting CAR-T therapy | Pediatric patients with relapsed/refractory ALL | T cells were edited to express CD19 CAR, infused back into patients | High response rate, durable response in some patients | Cytokine release syndrome, neurotoxicity | [174] |
Solid Tumors | Targeted genome editing of CCR4 gene | Patients with advanced solid tumors | CRISPR/Cas9 was used to target the CCR4 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [175] |
Melanoma | Targeted genome editing of NRAS gene | Patients with advanced NRAS-mutant melanoma | CRISPR/Cas9 was used to target the NRAS gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [176] |
Cholangiocarcinoma | Targeted genome editing of IDH1 gene | Patients with advanced IDH1-mutant cholangiocarcinoma | CRISPR/Cas9 was used to target the IDH1 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [177] |
Solid Tumors | Targeted genome editing of TP53 gene | Patients with advanced solid tumors | CRISPR/Cas9 was used to target the TP53 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [178] |
Myeloma | CD19-targeting CAR-T therapy | Patients with relapsed/refractory myeloma | T cells were edited to express CD19 CAR, infused back into patients | High response rate, durable response in some patients | Cytokine release syndrome, neurotoxicity | [179] |
Solid Tumors | Targeted genome editing of PD-1 gene | Patients with advanced solid tumors | CRISPR/Cas9 was used to target the PD-1 gene in tumor cells, followed by infusion of edited T cells | Enhances anti-tumor immunity by disrupting immune checkpoint pathway | Off-target effects, limited efficacy in some patients | [180] |
Solid Tumors | Targeted genome editing of MUC1 gene | Patients with advanced MUC1 + solid tumors | CRISPR/Cas9 was used to target the MUC1 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [181] |
Multiple Solid Tumors | Targeted genome editing of EGFR gene | Patients with advanced EGFR-mutant solid tumors | CRISPR/Cas9 was used to target the EGFR gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [165] |
Leukemia/Lymphoma | Targeted genome editing of CD22 gene | Patients with relapsed/refractory CD22 + leukemia/lymphoma | CRISPR/Cas9 was used to target the CD22 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [182] |
Solid Tumors | Targeted genome editing of PTEN gene | Patients with advanced PTEN-deficient solid tumors | CRISPR/Cas9 was used to target the PTEN gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [183] |
Multiple Solid Tumors | Targeted genome editing of PDCD1 gene | Patients with advanced solid tumors | CRISPR/Cas9 was used to target the PDCD1 gene in tumor cells, followed by infusion of edited T cells | Enhances anti-tumor immunity by disrupting immune checkpoint pathway | Off-target effects, limited efficacy in some patients | [184] |
Leukemia/Lymphoma | Targeted genome editing of TCR gene | Patients with relapsed/refractory leukemia/lymphoma | CRISPR/Cas9 was used to target the TCR gene in T cells, followed by infusion of edited T cells | Specific targeting of TCR gene for enhanced T-cell activity | Off-target effects, limited efficacy in some patients | [185] |
Leukemia/Lymphoma | CD19-targeting CAR-T therapy | Patients with relapsed/refractory leukemia/lymphoma | T cells were edited to express CD19 CAR, infused back into patients | High response rate, durable response in some patients | Cytokine release syndrome, neurotoxicity | [186] |
Solid Tumors | Targeted genome editing of HIF-1α gene | Patients with advanced HIF-1α-overexpressing solid tumors | CRISPR/Cas9 was used to target the HIF-1α gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [187] |
Non-small cell lung cancer | CRISPR/Cas9-mediated PD-1 knockout | Patients with advanced PD-L1 + non-small cell lung cancer | CRISPR/Cas9 was used to knock out the PD-1 gene in T cells, followed by infusion of edited T cells | Disrupts immune checkpoint pathway | Off-target effects, limited efficacy in some patients | [188] |
Multiple Solid Tumors | CRISPR/Cas9-mediated knockout of TGF-β receptor II | Patients with advanced TGF-β-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the TGF-β receptor II gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [189] |
Solid Tumors | CRISPR/Cas9-mediated knockout of DNMT1 | Patients with advanced solid tumors | CRISPR/Cas9 was used to knock out the DNMT1 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of epigenetic regulator | Off-target effects, limited efficacy in some patients | [190] |
Solid Tumors | CRISPR/Cas9-mediated knockout of LAP | Patients with advanced LAP-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the LAP gene in tumor cells, followed by infusion of edited T cells | Specific targeting of immunosuppressive mechanism | Off-target effects, limited efficacy in some patients | [191] |
Solid Tumors | CRISPR/Cas9-mediated knockout of AXL | Patients with advanced AXL-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the AXL gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [192] |
Solid Tumors | CRISPR/Cas9-mediated knockout of HLA class I | Patients with advanced HLA class I-deficient solid tumors | CRISPR/Cas9 was used to knock out the HLA class I genes in tumor cells, followed by infusion of edited T cells | Specific targeting of immune evasion mechanism | Off-target effects, limited efficacy in some patients | [193] |
Leukemia/Lymphoma | CRISPR/Cas9-mediated knockout of TCR and B2M | Patients with relapsed/refractory T-cell malignancies | CRISPR/Cas9 was used to knock out the TCR and B2M genes in T cells, followed by infusion of edited T cells | Disruption of T-cell receptor and MHC class I expression to prevent graft-versus-host disease and enhance anti-tumor activity | Off-target effects, limited efficacy in some patients | [194] |
Solid Tumors | CRISPR/Cas9-mediated knockout of β-catenin | Patients with advanced β-catenin-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the β-catenin gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [195] |
Leukemia/Lymphoma | CRISPR/Cas9-mediated knockout of CD7 | Patients with relapsed/refractory CD7 + leukemia/lymphoma | CRISPR/Cas9 was used to knock out the CD7 gene in T cells, followed by infusion of edited T cells | Specific targeting of B-cell antigen | Off-target effects, limited efficacy in some patients | [196] |
Solid Tumors | CRISPR/Cas9-mediated knockout of PSCA | Patients with advanced PSCA-expressing solid tumors | CRISPR/Cas9 was used to knock out the PSCA gene in tumor cells, followed by infusion of edited T cells | Specific targeting of tumor-associated antigen | Off-target effects, limited efficacy in some patients | [190] |
Solid Tumors | CRISPR/Cas9-mediated knockout of APOBEC3B | Patients with advanced APOBEC3B-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the APOBEC3B gene in tumor cells, followed by infusion of edited T cells | Specific targeting of mutagenic enzyme | Off-target effects, limited efficacy in some patients | [197] |
Solid Tumors | CRISPR/Cas9-mediated knockout of IL2RG | Patients with advanced IL2RG-deficient solid tumors | CRISPR/Cas9 was used to knock out the IL2RG gene in T cells, followed by infusion of edited T cells | Specific targeting of immunodeficiency gene | Off-target effects, limited efficacy in some patients | [198] |
Solid Tumors | CRISPR/Cas9-mediated knockout of ARID1A | Patients with advanced ARID1A-mutant solid tumors | CRISPR/Cas9 was used to knock out the ARID1A gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogenic driver mutation | Off-target effects, limited efficacy in some patients | [199] |
Solid Tumors | CRISPR/Cas9-mediated knockout of TRAC | Patients with advanced TRAC-deficient solid tumors | CRISPR/Cas9 was used to knock out the TRAC gene in T cells, followed by infusion of edited T cells | Specific targeting of immunodeficiency gene | Off-target effects, limited efficacy in some patients | [200] |
Solid Tumors | CRISPR/Cas9-mediated knockout of LAPTM4B | Patients with advanced LAPTM4B-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the LAPTM4B gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogene | Off-target effects, limited efficacy in some patients | [201] |
Solid Tumors | CRISPR/Cas9-mediated knockout of HPRT1 | Patients with advanced HPRT1-overexpressing solid tumors | CRISPR/Cas9 was used to knock out the HPRT1 gene in tumor cells, followed by infusion of edited T cells | Specific targeting of oncogene | Off-target effects, limited efficacy in some patients | [202] |