Table 2.
Ongoing and past clinical trials involving direct cellular administration of unmodified and modified γδ T cells, including study outcome (if available).
| ClinicalTrials.gov Identifier/reference | Status | Cell type(s) infused | Donor source | Cell source | Modification of cells, if applicable | Trial phase | Condition/disease | Outcome |
|---|---|---|---|---|---|---|---|---|
| (48) | Completed | Enriched in Vγ9Vδ2 T cells (Innacell™; single BrHPP stimulation followed by 2-week expansion in presence of IL-2 in vitro); infused with IL-2 | Autologous | PB | nil | 1 | Metastatic RCC | n = 10 Efficacy 6 SD: 60% 4 PD: 40% PFS: 25.7 weeks (5-111 weeks) Safety and toxicity DLT: 1 out of 3 patients treated at 8 x 10^9 cells |
| (49) | Completed | Activated by 2-methyl-3-butenyl-1-pyrophosphate and expansion in the presence of IL-2 until day 14 | Autologous | PB | nil | Not applicable | Advanced RCC | n=7 Efficacy 3 PR: 43% Safety and toxicity No serious adverse events observed. |
| (50) | Completed | Expanded using IL-2 and zoledronate | Autologous | PB | nil | 1 | NSCLC | n=10 Efficacy 3 SD: 30% 5 PD: 50% Safety and toxicity No serious adverse events observed. |
| (51) | Completed | Enriched in Vγ9Vδ2 T cells (zoledronate stimulation followed by 2-week expansion in presence of IL-2 in vitro); infused with zoledronate | Autologous | PB | nil | 1 | Breast cancer, cervical cancer and other solid tumors | n=18 Efficacy 1 CR: 6% 2 PR: 11% 3 SD: 17% PR and CR achieved with co-treatment. Safety and toxicity No DLT observed. |
| NCT02418481 | Completed | γδ T cells with or without DC-CIK cells | Autologous | PB | nil | 1 & 2 | Breast cancer | |
|
NCT02425735
(52) |
Completed | Vγ9Vδ2 T cells with or without DC-CIK cells | Autologous | PB | nil | 1 & 2 | Hepatocellular liver cancer (including CCA) | 1 case study published (allogeneic). Efficacy Positively regulated peripheral immune functions of the patient, depleted tumor activity, improved quality of life, and prolonged his life span. Safety and toxicity No adverse effects. |
| NCT02425748 | Completed | γδ T cells with or without DC-CIK cells | Autologous | PB | nil | 1 & 2 | Non small lung cancer (without EGFR mutation) | No published results. |
|
NCT03180437
(53) |
Completed | Vγ9Vδ2 T cells with or without IRE surgery | Allogeneic | PB | nil | 1 & 2 | Locally advanced pancreatic cancer | n=62 Efficacy Median OS: 14.5 months compared to 11 months without γδ T infusion Median PFS: 11 months compared to 8.5 months without γδ T infusion Safety and toxicity 14 serious adverse events (grade 3 and 4) observed that were likely due to IRE treatment and not γδ T cells |
|
NCT03183206, NCT03183219, NCT03183232
(54) |
Completed | Vγ9Vδ2 T cells expanded using zoledronate, IL-2, IL-15 and vitamin C for 12-14 days | Autologous | PB | nil | 1 & 2 | Breast cancer, liver cancer and lung cancer, respectively | n=132 Efficacy 18 patients (13.6%) showed response and prolonged survival Median OS (liver cancer patients): 23.1 months compared to 8.1 months in control group Median OS (lung cancer patients): 19.1 months compared to 9.1 months in control group Safety and toxicity No significant adverse events (immune rejection, GvHD or CRS) observed. |
|
NCT03790072
(55) |
Completed | Ex vivo expanded Vγ9Vδ2 T cells (OmnImmune®) using zoledronate and IL-2 | Allogeneic (matched or haploidentical family donors) | PB | nil | 1 & 2 | AML | n=7 Efficacy 1 CR: 14% 1 SD: 14% (eventually progressed) 1 MLFS: 14% Safety and toxicity No DLT and significant adverse effect (GvHD or neurotoxicity) observed. 1 patient suffered possible grade 1 CRS. |
| NCT04696705 | Recruiting | Ex-vivo expanded γδ T cells | Allogeneic (blood-related donor) | PB | nil | Early phase 1 | NHL, PTCL | No published results. |
| NCT04702841 | Recruiting | CAR γδ T cells | Autologous | PB | CD7 CAR | Early phase 1 | R/r CD7+ T cell-derived malignant tumors | No published results. |
| NCT03533816 | Recruiting | Expanded/activated γδ T cell, followed by depletion of αβ T-cells (INB-100) | Allogneneic (haploidentical donors) | PB | nil | 1 | AML, CML, ALL, MDS | n=7 Efficacy 7 CR: 100% PFS: 2.6 - 36 months Safety and toxicity No DLT observed. All patients experienced low grade (1–2) GvHD |
| NCT04165941 | Recruiting | γδ T cells (activated and gene modified) (INB-200) | Autologous | PB | MGMT-gene modified to be drug resistant | 1 | Glioblastoma multiforme | n=8 Efficacy Cohort 1 (single dose) PFS: 7.4-11.9 months OS: 9.6-17.7 months Cohort 2 (3 doses) PFS: 19.4-23.5 months Safety and toxicity No DLT and serious adverse events (CRS and ICANS) observed. Some grade 1-2 treatment emergent adverse events observed. |
| NCT04990063 | Recruiting | Tumor killer cells: mixed cocultures of NK cells & γδ T cells | Autologous | PB | nil | 1 | Advanced NSCLC | No published results. |
| NCT05015426 | Recruiting | γδ T cells (Artificial Antigen Presenting Cell-expanded donor T cells) | Allogeneic | Not stated | nil | 1 | AML | No published results. |
|
NCT04735471,
NCT04911478 |
Recruiting | Ex vivo activated and expanded Vδ1 T cells, followed by depletion of αβ T cells (ADI-001) | Allogeneic | PB | Anti-CD20 CAR (3H7-CD8 HTM-BBz) | 1 | Follicular lymphoma, MCL, MZL, burkitt lymphoma, mediastinal lymphoma, DLBCL, NHL | N=16 Efficacy 6 CR: 38% 1 PR: 6% 2 SD: 13% 5 PD: 31% Safety and toxicity No DLT, GvHD, Grade 3 or higher CRS or ICANS reported. |
| NCT05400603 | Recruiting | γδ T cells in combination with dinutuximab, temozolomide, irinotecan and zoledronate (Vδ2 T cells) | Allogeneic | PB | nil | 1 | R/r neuroblastoma (pediatric) | No published results. |
| NCT05653271 | Recruiting | Vδ2 T cells (ACE1831) or ACE1831 and obinutuzumab | Allogeneic | PB | anti-CD20 antibody conjugated | 1 | B cell lymphoma, NHL, DLBCL, primary mediastinal large B cell lymphoma, MZL, follicular lymphoma |
No published results. |
| NCT04764513 | Recruiting | Ex vivo expanded γδ T cells (expansion from same donors as HSCT) | Allogeneic | PB | nil | 1 & 2 | Hematological malignancies after allogeneic HSCT: AML, ALL, MDS, lymphoma |
No published results. |
| NCT04765462 | Recruiting | Ex vivo expanded γδ T cells (expansion from same donors as HSCT) | Allogeneic | Not stated | nil | 1 & 2 | Malignant solid tumour | No published results. |
| NCT05554939 | Recruiting | CAR γδ T cells | Allogeneic | PB | anti-CD19 CAR | 1 & 2 | R/r B cell NHL | No published results. |
| NCT05886491 | Recruiting | Enriched for Vδ1+ γδ T cells (GDX012) after lymphodepleting chemotherapy (fludarabine/cyclophosphamide) | Allogeneic | PB | nil | 1 & 2 | AML | No published results. |
| NCT03849651 | Recruiting | TCRαβ-depleted hematopoietic cell transplantation with additional memory cell DLI and selected use of blinatumomab | Allogeneic/haploidentical | PB | nil | 2 | ALL, AML, MDS, NK cell Leukemia, Hodgkin lymphoma, NHL, JMML, CML | No published results. |
| NCT05358808 | Recruiting | Vδ2 T cells (TCB-008) | Allogeneic | PB | nil | 2 | AML | No published results. |
| NCT05686538 | Recruiting | Innate donor lymphocyte infusion enriched in NK and γδ T cells | Allogeneic | PB/BM | nil | 2 & 3 | AML, MDS | No published results. |
| NCT05388305 | Recruiting | CAR γδ T cells | Allogeneic | Not stated | anti-CD123 CAR | Not applicable | R/r AML | No published results. |
| NCT05302037 | Not yet recruiting | CAR γδ T cells | Allogeneic | PB | NKG2DL-targeting CAR | 1 | Advanced solid tumours or haematological malignancies | No published results. |
| NCT03939585 | Not yet recruiting | NK/γδ T cell-enriched product (donor lymphocytes depleted of TCR-αβ T cells and B cells) | Allogeneic (HLA matched sibling donors or partially matched, related haploidentical donors) | PB | nil | 1 | Allogeneic stem cell transplant candidate AML, ALL, MDS, MPN, LPD |
No published results. |
| NCT04806347 | Not yet recruiting | TCRαβ+/CD19+ depleted HSC graft | Allogeneic (closely matched unrelated donors or haploidentical related donors) | PB | nil | 1 | Blood disease | No published results. |
| NCT05664243 | Not yet recruiting | γδ T cells (DeltEx) (INB-400) | Allogeneic | PB | genetically-modified (drug resistance immunotherapy) | 1 & 2 | Recurrent or newly diagnosed glioblastoma | No published results. |
| NCT00562666 | Terminated | γδ T cells | Autologous | PB | nil | 1 | HCC | No published results. |
| NCT05001451 | Terminated (business decision, not related to safety) | Enriched for Vδ1+ γδ T cells (GDX012) | Allogeneic | PB | nil | 1 | AML | No published results. |
| NCT05628545 | Withdrawn (COVID Pandemic) | γδ T cells (GDKM-100) | Allogeneic | Not stated | nil | 1 & 2 | Advanced HCC | No published results. |
| NCT02459067 | Terminated | γδ T cells (ImmuniCell®) | Autologous | PB | nil | 2 | Malignant melanoma, NSCLC, RCC | No published results. |
| NCT04700319 | Unknown | CAR γδ T cells | Autologous | PB | CD19/CD20 CAR | Early phase 1 | Advanced CD19/CD20+ B cell line recurrent or refractory haematological malignancies | No published results. |
| NCT04028440 | Unknown | γδ T cells | Autologous | PB | nil | Early phase 1 | NHL, r/r B cell NHL, CLL, PTCL | No published results. |
| NCT04518774 | Unknown | Ex-vivo expanded γδ T cells | Allogeneic (blood-related donor) | PB | nil | Early phase 1 | HCC | No published results. |
| NCT02656147 | Unknown | CAR γδ T cells | Allogeneic | Not stated | Anti-CD19-CAR | 1 | Leukemia, lymphoma | No published results. |
| NCT04008381 | Unknown | Ex-vivo expanded γδ T cells | Allogeneic (blood-related donor) | PB | nil | 1 | AML | No published results. |
| NCT04107142 | Unknown | CAR γδ T cells | Allogeneic/haploidentical | PB | NKG2DL-targeting CAR | 1 | Colorectal cancer, TNBC, sarcoma, NPC, prostate cancer, gastric cancer | No published results. |
| NCT02585908 | Unknown | γδ T cells with or without CIK cells | Autologous | PB | nil | 1 & 2 | Gastric cancer | No published results. |
| NCT04796441 | Unknown | CAR γδ T cells | Allogeneic | PB | anti-CD19 CAR | Not applicable | Relapsed AML | No published results. |
| NCT03885076 | Unknown | CAR Vδ2 T cells | Autologous | PB/BM | anti CD33 CAR | Not applicable (observational study) | AML (except M3) | No published results. |
DC, dendritic cells; CIK, cytokine-induced killer cells; IRE, irreversible electroporation; HSCT, hematopoietic stem cell transplantation; HSC, hematopoietic stem cell; HLA, human leukocyte antigen; PB, peripheral blood; BM, bone marrow; CAR, chimeric antigen receptor; HCC, hepatocellular carcinoma; CCA, cholangiocarcinoma; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; RCC, renal cell cancer; r/r, relapsed or refractory; NHL, non-Hodgkin lymphoma; PTCL, peripheral T cell lymphoma; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; ALL, acute lymphoblastic leukemia; T-ALL, T-cell acute lymphoblastic leukemia; TNBC, triple-negative breast cancer; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasm; LPD, lymphoproliferative disorders; MCL, mantle-cell lymphoma; MZL, marginal zone lymphoma; DLBCL, Diffuse large B cell lymphoma; NPC, nasopharyngeal carcinoma; JMML, Juvenile myelomonocytic leukemia; EGFR, epidermal growth factor receptor; TAC, T cell antigen coupler; CR, complete response; PR, partial response; SD, stable disease; MLFS, morphologic leukemia-free state; PFS, progression-free survival; OS, overall survival; DLT, dose-limiting toxicity; CRS, cytokine release syndrome; GvHD, graft-versus-host disease; ICANS, immune effector cell-associated neurotoxicity syndrome.