Table 1.
A summary of the clinical applications of cell-based therapies implemented in clinical trials in treating a number of diseases
| Cell | Target Antigen | Trial | Aim | Product | Route of Delivery | Antigen Loss | TME | Toxicity | Patient Outcome |
|---|---|---|---|---|---|---|---|---|---|
| CAR-T | IL13Rα2 |
NCT00730613 City of Hope 66, 68 |
First to evaluate intracranial delivery of IL13Rα2 CAR in rGBM | IL13(E13Y)-CD3ζ CD8+ CTL clones |
ICT | IL13Rα2 negative/low (1 patient tested) | Transient inflammatory response/necrosis at tumor site by MRI | No DLTs | 3 pts evaluated Median OS 10.9 mo Increased necrotic volume at treatment site (1 pt) Decreased IL13Rα2 expression (1 pt) |
| CAR-T | IL13Rα2 |
NCT01082926 City of Hope 67 |
First off-the-shelf allogeneic CAR T cells for rGBM. Evaluated feasibility of [18F]FHBG gene reporter imaging to monitor T-cell distribution in rGBM | IL13(E13Y)-CD3ζ [18F]FHBG HSV1-tk Glucocorticoid-receptor-depleted allogeneic CD8+ CTL clone |
ICT | Not reported | Not reported | No DLTs | 6 pts evaluated [18F]FHBG gene reporter allowed longitudinal imaging of ICT CAR-T Clinical outcomes not reported |
| CAR-T | IL13Rα2 |
NCT02208362 City of Hope69 |
Evaluate safety of ICV and dual ICT-ICV CAR delivery in rGBM | IL13(E13Y)-41BBζ Memory-derived T cells |
ICT, ICV and dual ICT-ICV | IL13Rα2 negative/low tumors (1 patient reported) | Increased CD3+ CD14+ and CD15+ immune cells and inflammatory cytokines | No DLTs | Case study demonstrated CAR-Ts mediate complete response that was durable for 7.5 mo |
| CAR-T | EGFRvIII |
NCT02664363 Duke University |
Utilizing TMZ-DI as a preconditioning lymphodepleting regimen and treatment for GBM | KLuc-EGFRvIII-expressing T cells | IV | Not reported | EGFRvIII-positive GBM. Pre-conditioned with TMZ-DI | Not reported | Terminated, July 2020, no results available |
| CAR-T | HER2 |
NCT04660929 Carisma Therapeutics, Inc. https://pubmed.ncbi.nlm.nih.gov/32361713/ https://www.nature.com/articles/d43747-020-01096-y https://clinicaltrials.gov/ct2/show/NCT04660929 |
Phase 1 study of CAR macrophages in HER2 overexpressing solid tumors. | THP-1 cell line transduced with a first-generation anti-CD19 CAR encoding the CD3ζ intracellular domain. | IV | Not reported | CAR macrophages are activated by tumor-associated antigen engagement with the CAR, signaling via CD3-ζ to phagocytose the tumor cell and release cytokines and chemokines that ‘warm up’ the TME. | Not reported | Ongoing |
| CAR-Macrophage | Mesothelin |
NCT03608618 MaxCyte, Inc. https://clinicaltrials.gov/ct2/show/NCT03608618 |
Phase 1 study on the use of of MCY-M11 as treatment for platinum resistant high grade serous adenocarcinoma and peritoneal mesothelioma | Mesothelin-CAR-expressing mRNA-targeted CAR macrophages | Intraperitoneal | Not reported | Not reported | Not reported | Ongoing |
| CAR-NK | CD33 |
NCT02944162 PersonGen BioTherapeutics (Suzhou) Co., Ltd. https://clinicaltrials.gov/ct2/show/NCT02944162 |
Study genetically engineered NK92 cell therapy to treat CD33 positive acute myeloid leukemias | Anti-CD33 CAR-NK cells | IV | Not reported | Not reported | Not reported | Recruitment status unknown |
| CAR-NK | NKG2D ligands |
NCT03415100 The Third Affiliated Hospital of Guangzhou Medical University https://www.clinicaltrials.gov/ct2/show/NCT03415100 |
Study to evaluate the safety and feasibility of CAR-NK cell treatment for metastatic solid tumors. | NKG2D-Ligand Targeted CAR-NK Cells | IV | Not reported | Not reported | Not reported | Recruitment status unknown |
| CAR-NK | CD19+ |
NCT03056339 M.D. Anderson Cancer Center https://clinicaltrials.gov/ct2/show/NCT03056339 |
Study the use of CAR-CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells to treat relapsed/refractory CD19+ B lymphoid malignancies. | CAR-CD19-CD28-zeta-2A-iCasp9-IL15-transduced CB-NK cells | IV | Not reported | Not reported | Not reported | Actively recruiting |
| NSC | N/A |
NCT01172964 City of Hope |
Determine the safety and feasibility of intracerebral administration of NSCs with oral 5-FC to treat recurrent high-grade gliomas. | E. coli CD-expressing genetically modified neural stem cells | ICT | Not reported | Not reported | Not reported | Completed, no results posted |
| NSC | N/A |
NCT03072134 Northwestern University |
Phase I study of neural stem cell based virotherapy in combination with standard radiation and chemotherapy to treat with newly diagnosed malignant glioma | NSC-CRAd-Survivin-pk7 | ICT | Not reported | Not reported | Not reported | Ongoing |
| NSC | N/A |
NCT03629275 ReNeuron, Ltd. |
Study of the use of CTX0E03 neural stem cells to treat moderate to moderately severe disability as a result of an ischemic stroke | CTX0E03 neural stem cells | ICT | Not reported | Not reported | Not reported | Ongoing |
| Dendritic | Autologous tumor cells |
NCT04277221 Safe Save Medical Cell Sciences & Technology Co.,Ltd. |
Phase III study on the use of ADCTA immunotherapy with standard therapy to treat recurrent GBM. | ADCTA-SSI-G1 | Subcutaneous | Not reported | Not reported | Not reported | Actively recruiting |
| Dendritic | MGMT-promotor methylation |
NCT03548571 Oslo University Hospital |
Study of dendritic cell therapy to treat IDH wild-type, MGMT-promotor methylated glioblastoma | Dendritic cells transfected with mRNA of autologous tumor stem cells, survivin, and hTERT | Intradermal | Not reported | Not reported | Not reported | Actively recruiting |