Table 3 Clinical trials of CRISPR-based cancer therapy

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

NCT04420539

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

NCT03939026

Renal Cell Carcinoma

Biological: CTX130

All patients with relapsed or refractory Renal Cell Carcinoma

CTX130 for Renal Cell Carcinoma; Phase 1, Open Label

Targets RCC specifically, innovative CAR T-cell therapy

Early phase, potential for adverse events

NCT04438083

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

NCT02209376

Non-Small-Cell Lung 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

[2]

Acute Myeloid Leukemia

FT538-targeting CAR-T therapy

Patients with relapsed/refractory AML

the use of FT538, a gene-edited CAR-T therapy targeting CD33 and CD19, in patients with relapsed/refractory AML and multiple myeloma

Target specificity, potential for durable response

Cytokine release syndrome, neurotoxicity

NCT04614636

Cervical 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

[3]

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

[4]

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

[5]

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

[6]

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

[7]

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

[8]

Myeloma

Integrated PD1-BCMA-CART

Patients with relapsed/refractory myeloma

Non-viral site-directed integrated PD1-BCMA-CART in adult patients

High response rate, durable response in some patients

Cytokine release syndrome, neurotoxicity

NCT05308875

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

[9]

Metastatic Breast Cancer

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

[10]

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

NCT05201910

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

[11]

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

[12]

Lymphoma Cells

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

NCT04005053

Hematologic Malignancy, Solid Malignancy

Non Interventional, Observational

All patients

Observational study to assess adverse events, serious adverse events, and events of special interest related to CRISPR CAR T cellular therapy. Also, evaluates overall survival and duration of remission/response

Broad patient inclusion, potential for long-term data collection

Observational, may not provide direct treatment benefits

NCT06208878

Multiple Myeloma, Melanoma, Synovial Sarcoma

Biological: NY-ESO-1 redirected autologous T cells, Drugs: Cyclophosphamide, Fludarabine

All patients

Evaluates safety, manufacturing feasibility, and clinical responses of NYCE T cells in multiple cancers

Targets NY-ESO-1, a known cancer-testis antigen, potential for multiple cancer types

Terminated study, may have limited data on long-term efficacy and safety

NCT03399448

Neurofibromatosis Type 1, Tumors of the CNS

Diagnostic Test: Collection of Stem Cells

All patients

Observational study to identify mutations in NF1 genes and measure neuronal characteristics of derived neurons. Uses CRISPR/CAS9 for genetic modifications

Provides insight into genetic mutations and potential therapeutic targets

Observational, not treatment-focused

NCT03332030

B-cell Lymphoma, Non-Hodgkin Lymphoma, B-cell Malignancy

Biological: CTX112

All patients

Phase 1/2 study evaluating safety, efficacy, and response rates of CTX112 in B-cell malignancies

Potential new treatment option

Limited to early-phase study, potential side effects

NCT05643742

Relapsed/Refractory Multiple Myeloma

Biological: CB-011

All patients

Phase 1 study on CRISPR-edited anti-BCMA CAR-T cells, focusing on dose-limiting toxicities and overall response rate

Innovative use of CRISPR technology

Early-phase, potential unknown risks

NCT05722418

Esophageal Cancer

Other: PD-1 Knockout T Cells

All patients

Interventional study assessing the efficacy and adverse events of PD-1 knockout T cells in treating esophageal cancer

Could offer a new therapeutic pathway

Safety and long-term efficacy concerns

NCT03081715

Solid Tumor, Adult, EGFR Overexpression

Biological: TGFβR-KO CAR-EGFR T Cells

All patients

Phase 1 study on the safety and response rates to TGFβR-KO CAR-EGFR T cell therapy in EGFR-positive tumors

Targets a specific cancer marker, potentially improving efficacy

Phase 1 study, limited safety and efficacy data

NCT04976218

Acute Myeloid Leukemia, in Relapse or Refractory

Drug: CB-012

All patients

Phase 1 study on CRISPR-edited anti-CLL-1 CAR-T cells, focusing on dose-limiting toxicities and overall response rate

Offers a targeted approach for a difficult-to-treat cancer

Early-phase study with inherent risks of novel therapy

NCT06128044

Advanced Stage EBV Associated Malignancies

Drugs: Fludarabine, Cyclophosphamide, Interleukin-2

All patients

Phase 1/2 study evaluating PD-1 knockout EBV-CTLs for safety and efficacy in EBV-associated malignancies

Innovative immunotherapy approach

Unknown status, potential risks and side effects

NCT03044743

T Cell Lymphoma

Biological: CTX130

All patients

Phase 1 study evaluating safety and efficacy of CTX130 in T or B cell malignancies, including dose escalation and cohort expansion

Potential new option for lymphoma treatment

Early-phase, possible adverse effects

NCT04502446

Lymphoma, Non-Hodgkin, Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Genetic: CB-010, Drugs: Cyclophosphamide, Fludarabine

All patients

Phase 1 study on CRISPR-edited anti-CD19 CAR-T cells for B-cell non-Hodgkin lymphoma, assessing toxicities and tumor response

Utilizes CRISPR technology for targeted therapy

Phase 1, risks of new treatment modalities

NCT04637763

Solid Tumors

Biological: CTX131

All patients

Phase 1/2 study on CTX131 in relapsed or refractory solid tumors, assessing adverse events and objective response rate

Investigates new treatment for solid tumors

Limited to early-phase trials, potential side effects

NCT05795595

B Acute Lymphoblastic Leukemia (B-ALL)

Drug: PBLTT52CAR19

All patients with B-ALL seeking remission

TT52CAR19 Therapy for B-ALL; Phase 1, Open Label

Targets B-ALL specifically, aiming for remission

Early phase with limited patient data

NCT04557436

CD5 + Relapsed/Refractory Hematopoietic Malignancies, CLL, MCL, etc

Biological: CT125A cells; Drug: Cyclophosphamide, fludarabine

All patients with CD5 + hematopoietic malignancies seeking treatment for relapse/refractory conditions

Safety and Efficacy of CT125A Cells; Early Phase 1, Open Label

Addresses multiple CD5 + malignancies, comprehensive treatment approach

Early phase, potential for unknown AEs

NCT04767308

Multiple Myeloma

Biological: CTX120

All patients with relapsed or refractory Multiple Myeloma

CTX120 Study for Multiple Myeloma; Phase 1, Open Label

Potential for durable response in MM treatment

Risks associated with novel therapy, limited data on long-term outcomes

NCT04244656

Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma

Biological: PACE CART19

All patients with CD19 + leukemia and lymphoma seeking alternative treatments

PACE CART19 for CD19 + malignancies; Phase 1, Open Label

Innovative CRISPR-edited T-cell therapy, broad application

Withdrawn status limits data availability

NCT05037669

Metastatic Non-small Cell Lung Cancer

Drug: Cyclophosphamide; Other: PD-1 Knockout T Cells

All patients with metastatic NSCLC seeking new therapeutic options

PD-1 Knockout T Cells for NSCLC; Phase 1, Completed with results

Demonstrated safety and preliminary efficacy

Specific to PD-1 + , limited to metastatic stage

NCT02793856

Relapsed/Refractory T-cell Acute Lymphoid Leukaemia

Biological: Cryopreserved BE CAR7 T cells

All patients with T-cell ALL seeking remission ahead of allo-SCT

Base Edited CAR7 T Cells for T-cell Malignancies; Phase 1, Open Label

Novel base editing approach, focused on remission

Early phase, potential unknown risks

NCT05397184

High Grade Ovarian Serous Adenocarcinoma, Stage III

Other: Biospecimen Collection, Laboratory Biomarker Analysis, Device: Lavage

Female patients with advanced ovarian cancer for diagnostic purposes

Lavage for Ovarian Cancer Diagnosis; Not Applicable, Terminated with results

Non-invasive diagnostic approach, early detection

Terminated, may indicate limited feasibility or efficacy

NCT03606486

B Cell Leukemia, B Cell Lymphoma

Biological: Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells

All patients with B cell leukemia or lymphoma seeking new treatments

Universal Dual Specificity CAR-T for Leukemia and Lymphoma; Phase 1/2, Open Label

Dual specificity may increase efficacy

Unknown status, risks associated with broad application

NCT03398967

B Cell Leukemia, B Cell Lymphoma

Biological: UCART019

All patients with CD19 + leukemia and lymphoma seeking alternative therapies

UCART019 for CD19 + malignancies; Phase 1/2, Open Label

Utilizes universal CAR T cells, broad potential application

Unknown status, early phase with inherent risks

NCT03166878

Acute Myeloid Leukemia (AML)

Biological: Donor-derived CD34 + HSC with CRISPR/Cas9-mediated CD33 deletion, Drug: Gemtuzumab Ozogamicin

All patients with Relapsed/Refractory AML

Interventional study aiming to test the engraftment of gene-edited CD34 + HSC and assess dose-limiting toxicity

Potentially improves therapeutic index of CD33-directed therapy

Risk of toxicities as per CTCAE v5.0

NCT05662904

Leukemia, Myeloid, Acute

Genetic: VOR33

All patients previously participating in a VOR33 study

Observational study to evaluate long-term safety and efficacy of VOR33

Offers insight into long-term effects and efficacy

Limited by observational design

NCT05309733

Acute Myeloid Leukemia

Genetic: NTLA-5001

All patients enrolled in the study

Interventional study evaluating NTLA-5001's safety and effectiveness

Potential novel treatment for AML

Terminated, possibly indicating issues

NCT05066165

Nasopharyngeal Carcinoma

Diagnostic Test: EBV antibodies test, EBV DNA test

Male patients for screening

Observational study assessing diagnostic tests' predictive values and sensitivity

Could improve early detection

Specific to male patients, limiting broader applicability

NCT05447169

Advanced Breast Cancer

Drug: AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells

All patients with Advanced Breast Cancer

Interventional study on the safety and efficacy of CAR-T cell therapy

Innovative approach for advanced cases

Potential adverse events and toxicities

NCT05812326

Non-hodgkin Lymphoma, B Cell

Biological: Autologous CD19-STAR-T cell, Drugs: Fludarabine, Cyclophosphamide

All patients with r/r B-NHL

Interventional study assessing adverse events, DLTs, and MTD

Targets B-cell lymphoma specifically

Phase 1/2, indicating early research stage

NCT05631912

Hormone Refractory Prostate Cancer

Biological: PD-1 Knockout T Cells, Drug: Cyclophosphamide, IL-2

Male patients with castration-resistant cancer

Observational study on the safety and efficacy of PD-1 Knockout T Cells

Potential new therapy for resistant cases

Withdrawn, questioning viability

NCT02867345

Advanced Hepatocellular Carcinoma

Procedure: Transcatheter arterial chemoembolization, Biological: PD-1 knockout engineered T cells

All patients with Advanced Hepatocellular Carcinoma

Interventional study to assess safety and response rate

Combines TACE with immunotherapy

Early phase research

NCT04417764

Invasive Bladder Cancer Stage IV

Biological: PD-1 Knockout T Cells, Drug: Cyclophosphamide, IL-2

All patients with Stage IV Invasive Bladder Cancer

Interventional study on safety and response rate

Targets advanced bladder cancer specifically

Withdrawn, raising concerns about feasibility

NCT02863913

Non Hodgkin's Lymphoma

Biological: TRAC and Power3 Genes Knock-out Allogeneic CD19-targeting CAR-T cell, Drugs: Fludarabine, Cyclophosphamide

All patients with r/r B-NHL

Interventional study evaluating adverse events, RP2D, and ORR

Innovative CAR-T cell therapy approach

Still in early phase research

NCT06014073

Metastatic Renal Cell Carcinoma

Biological: PD-1 Knockout T Cells, Drug: Cyclophosphamide, IL-2

All patients with Metastatic Renal Cell Carcinoma

Interventional study on the safety and tolerability of PD-1 Knockout T cells

Offers a new treatment avenue for metastatic cases

Withdrawn, suggesting potential issues

NCT02867332

Human Papillomavirus-Related Malignant Neoplasm

Biological: TALEN, Biological: CRISPR/Cas9

Female patients

Evaluates the safety and efficacy in treating HPV-related cervical intraepithelial neoplasia with TALEN and CRISPR/Cas9. Measures include adverse events, HPV DNA titers, and cervical cytological changes

Targeted intervention for HPV, potential for HPV eradication

Limited to female patients, early phase study

NCT03057912

Solid Tumor, Adult

Biological: anti-mesothelin CAR-T cells

All patients

Study focuses on adverse events and clinical responses to anti-mesothelin CAR-T cell infusions in mesothelin positive solid tumors

Directly targets tumor-specific antigen, potential for specific efficacy

Early phase study, outcomes and long-term effects uncertain

NCT03545815

Gastrointestinal Cancers

Drug: Cyclophosphamide, Fludarabine, Biological: TIL

All patients

Evaluates the maximum tolerated dose, efficacy, and safety of autologous lymphocytes with CISH gene knockout in metastatic gastrointestinal cancers

Innovative genetic engineering approach, targets multiple cancer types

Non-randomized, potential adverse events related to treatment

NCT04426669

Solid Tumor, Adult

Biological: Mesothelin-directed CAR-T cells

All patients

Studies adverse events and clinical responses to mesothelin-directed CAR T cells infusion in multiple solid tumors

Targets specific tumor antigen, potential for broad application

Early phase study, specific adverse events associated with CAR-T therapy

NCT03747965

Neoplasms, Pancreatic

Drug: GSK3145095, Pembrolizumab

All patients

Assesses adverse events and efficacy of GSK3145095 alone and in combination with pembrolizumab in advanced solid tumors. Includes extensive safety profiling

Combination therapy potential, broad patient inclusion

Terminated study, results may be limited

NCT03681951

B-cell Malignancies

Biological: CTX110

All patients

Evaluates the incidence of adverse events, objective response rate, and duration of response with CTX110 in relapsed/refractory B-cell malignancies

Targeted therapy for B-cell malignancies, potential for durable responses

Phase 1/2 study, adverse events as a primary consideration

NCT04035434

Leukemia, Lymphoma

Genetic: XYF19 CAR-T cell, Drugs: Cyclophosphamide, Fludarabine

All patients

Assesses adverse events and maximum tolerated dose of XYF19 CAR-T cells in CD19 + leukemia or lymphoma

Specific targeting of CD19 + cells, innovative CAR-T approach

Limited to leukemia/lymphoma, potential severe CAR-T related adverse events

NCT04037566

Non-Small-Cell Lung Cancer

Drug: Fludarabine, Cyclophosphamide, Biological: CISH Inactivated TIL

All patients

Phase I/II study assessing safety, efficacy, ORR, and PFS of CISH inactivated TILs in NSCLC treatment

Innovative use of TILs, potential for significant efficacy in NSCLC

Phase 1/2, potential adverse events from treatment

NCT05566223