Exploration of Immunology

Table 3. Administration of γδ T cells in clinical trials as an immunotherapeutic tool for CRC and some solid tumors.

Study title	NCT number conditions	Phase of study status	Mechanism of action	Interventions, route of administration, lymphodepletion, enrollment estimated	Sponsor, study type, first posted, last verified	Primary and secondary endpoints
A Safety and Efficacy Study of Allogeneic CAR Gamma-Delta T Cells in Subjects with Relapsed/Refractory Solid Tumors	NCT06150885 Solid tumors CRC, TNBC, GBM, NSCLC	Phase I Phase IIa Recruiting	Nanobodies CAR BiTe targeting PD-L1, HLAG Elimination of tumor cells bearing inhibitory receptors PD-L1 and/or HLA-G	CAR001: HLA-G-CAR. BiTE allo γδ T cells Intravenous LD: NR N = 60	Ever Supreme Bio Technology Co., Ltd. Interventional 2023-11-29 2024-09	Safety Potential efficacy
ACE2016 in Adult Subjects With Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR)	NCT06415487 Locally advanced metastatic solid tumors	Phase I Recruiting	Killing tumor cells and inhibition ICB	ACE2016: allo γδ T cells Pembrolizumab: anti-PD-1 Intravenous LD: Cyclo, Flud N = 30	Acepodia Biotech, Inc. Interventional 2024-05-16 2025-06	Safety
Haplo/Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells for Relapsed or Refractory Solid Tumour	NCT04107142 CRC TNBC GC Sarcoma	Phase I Unknown status	NKG2DL (MICA/B, ULBP1-6) Killing tumor cells	CTM-N2D: alloNKG2DL-CAR-γδ T cells Intravenous LD: NR N = 10	CytoMed Therapeutics Pte Ltd. Interventional 2019-09-27 2019-09	Safety DLT Adverse effects
Study of SUPLEXA in Patients With Metastatic Solid Tumours and Haematologic Malignancies	NCT05237206 Metastatic solid tumors CRC, PC, others	Phase I Completed WITH RESULTS Serious AE n = 6/35 Other AE n = 25/35	Antitumor activity	Biological: SUPLEXA A cell mixture comprised predominantly of NK, NK-T, αβ T and γδ T cells stored in cryogenic media Intravenous LD: NR N = 46	Alloplex Biotherapeutics Inc. Interventional 2022-02-14 2025-08	Safety and tolerability efficacy
First-in-Human Study of ICT01 in Patients With Advanced Cancer	NCT04243499 Solid tumor CRC, bladder cancer, BC, GC, melanoma, PDAC hematological malignancies	Phase I Phase II Actively enrolled N = 292	Activation of γδ T cells and inhibition of ICB	IV ICT01 hBTN3A mAb plus anti-PD-1 pembrolizumab Intravenous LD: NR N = 292	ImCheck Therapeutics Interventional 2020-01-28 2026-01	Safety Tolerability DCR using RECIST Control rate using RECIL
Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients With Advanced Solid Tumors (EVICTION-2)	NCT05307874 Solid tumor CRC, bladder cancer, BC, GC, melanoma, PDAC hematological malignancies	Phase I Phase II Actively enrolled	Activation of γδ T cells and inhibition of ICB PD-1	IV ICT01 hBTN3A mAb plus low doses of IL-2 subcutaneously plus anti-PD-1 pembrolizumab Intravenous LD: NR N = 56	ImCheck Therapeutics Interventional	Safety AE DCR
Safety Study for a Gamma Delta T Cell Product Used With Low Dose Radiotherapy in Patients With Locally Advanced or Metastatic NSCLC or Solid Tumors With Bone Metastases	NCT06069570 Carcinoma, NSCLC, bone metastasis	Phase I Recruiting	Killing of tumor cells	KB-GDT-01 allo-γδ T cells Low dose of radiotherapy Intravenous LD: NR N = 48	Kiromic BioPharma Inc. Interventional 2023-10-06 2025-03	Safety tolerability AE, MTD, MAD ORR, PFS OS, TTP TTR, DCR
Allogeneic NKG2DL-targeting CAR γδ T Cells (CTM-N2D) in Advanced Cancers (ANGELICA)	NCT05302037 Refractory cancers Solid tumor hematological malignancies	Phase I Recruiting	Killing of tumor cells expressing NKG2DL (MICA/B, ULBP1-6)	Allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells (CTM-N2D) Intravenous LD: NR N = 12	CytoMed Therapeutics Pte Ltd. Interventional 2022-03-31 2024-11	Safety DLT AE PFS OS
A Study of PF-08046052/SGN-EGFRd2 in Advanced Solid Tumors	NCT05983133 CRC HNSCC NSCLC PDAC	Phase I Recruiting	Killing of EGFR⁺ tumor cells activating specifically Vδ2 TCR	Bispecific γδ T-cell engager LAVA1223 anti-EGFR-Vδ2 TCR Intravenous N = 68	Seagen, a subsidiary of Pfizer 2023-08-09 2026-04	Safety PFS OS
UTAA06 Injection for Treatment of Advanced Malignant Solid Tumors	NCT06372236 Advanced solid tumors	Phase I	Targeting B7-H3⁺ tumor cells	B7-H3 CAR-Vδ1 T cells Intravenous N = 10	Peking University 2024-04-17 2025-05	Safety MTD PK

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The table has been obtained from the https://clinicaltrials.gov/ website, accessed on 26th May 2026. AE: adverse events; BC: breast carcinoma; Cyclo: cyclophosphamide; DCR: disease control rate; DLT: dose limiting toxicity; Flud: fludarabine; GC: gastric cancer; GBM: glioblastoma; HNSCC: head and neck squamous cell carcinoma; ICB: immune check point; LD: lymphodepletion; MTD: maximum tolerated dose; MDA: maximum administered dose; NSCLC: non-small cell lung cancer; NR: not reported; ORR: objective response rate; PDAC: pancreatic adenocarcinoma; PC: prostate carcinoma; PFS: progression free survival; PK: pharmacokinetics; OS: overall survival; TTR: Time to Treatment Response; TTP: Time to Progression; TNBC; triple negative breast carcinoma; MICA/B: major histocompatibility complex class I (MIC) related molecules A and B; ULBP1-6: UL-16 binding proteins 1-6.

Declarations

Acknowledgments

All the figures have been designed from the templates of Anatomy and Human Body and Cellular Biology series of Smart Servier Medical Art (https://smart.servier.com/).

Author contributions

AP: Conceptualization, Investigation, Validation, Supervision, Writing—original draft, Writing—review & editing. The author read and approved the submitted version.

Conflicts of interest

The author declares that he has no conflicts of interest.

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The manuscript has been supported by the grant AIRCIG21648 to AP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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