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| Paper | Type of paper | N of patients/animals and study design | Results |
| | | Patients (n) | Animals (n) | Laboratory research | |
|
| Harrer D.C. et al. BMC Cancer (2017) | Research | NA | NA | Isolated γδ T cells transfected through mRNA electroporation with a gp100/HLA-A2-specific TCR and an MCSP-specific CAR. | Zoledronic acid-mediated expansion of γδ T cells directly
from PBMC is more efficient than expanding MACS isolated
γδ T cells
RNA-transfected γδ T cells responded to melanoma cells
with antigen-specific
cytokine secretion and tumor cell lysis, and retained their intrinsic cytotoxic activity towards
melanoma cells after electroporation |
|
| Yang J. et al. Fron. Oncol (2017) | Clinical | n. 8 patients with stage III in-transit melanoma treated with IL-BCG | NA | NA | Vγ9Vδ2 T cells play a role in IL-BCG-induced melanoma regressions. |
|
Hodgins N.O. et al,
Journal of Controlled Release (2016) | Research | NA | NSG mice
L-ZOL (toxicity assessment)
L-ALD + γδ T cells (efficacy assessment) | In vitro cell lines A375Ppuro | (i) In vitro, zoledronate and alendronate + Vg9Vd2 T-cells determined a significant and dose-dependent reduction in tumour cell viability.
(ii) In vivo, combined injection of alendronate and γδ T cells delayed tumour growth in an experimental metastatic lung mouse model
|
|
| Wang X. et al. Cancer Cell. (2015) | Research | NA | C57BL/6j (B6; H2Kb), BALB/c
(H2Kd), IFN-γ−/−, Prf1−/−, and Rag2IL2Rg doubly deficient mice. MyD88KO mice. IL-36R −/− mice (C57BL/6-Il1rl2<tm1Hblu>) | B16 and 4T1 cells
primary lymphocyte culture from C57BL/6 mice. | (i) IL-36γ effectively promoted IFN-γ production by γδ T and NK cells.
(ii) Tumoral expression of IL-36γ greatly inhibited tumor growth and metastasis in vivo, mainly through IFN-γ.
(iii) IL-36γ can boost the efficacy of tumor vaccination |
|
| Nieda M. Experimental Dermatology, (2015) | Research | NA | NA | PBMCs from HDs and Pts with metastatic melanoma (stage IV).
Vγ9Vδ2 (or CD8+) T cells stimulated with autologous CD56 high+ IFN-DCs or mIL-4DCs in the presence of zoledronate (1 lM) and IL-2 (1000 U/ml) for 10–14 days.
| CD56 high+ IFN-DCs efficiently promote the expansion of
CD56+ Vγ9Vδ2 T cells in the presence of zoledronate and IL-2. |
|
Conlon K.C. et al, JCO. (2015)
| Clinical | n. 11 Patients with metastatic Melanoma were treated with rhIL15 and frequency and cytokines released were analyzed (phase I study). | NA | NA | There was rhIL15-mediated activation of monocytes, NK and γδ T cells.
No objective remissions in all patients, with best response being stable disease. |
|
Gehrmann U. et al, Cancer Res. (2013)
| Research | NA | C57Bl/6, Vα14-Ca-/- and CD1d-/- mice. Exosomes loaded with αGC + OVA were used to treat the tumor-bearing mice and evaluate tumor growth. | | (i) Exosomes loaded with αGC and OVA[Exo(αGC-OVA)] induce an early iNKT-cell response, dendritic cell, MZB cell activation as well as NK- and γδ T-cell activation and proliferation in vivo
(ii) Exo(αGC-OVA) also decrease tumor growth and induce T-cell
infiltration in a mouse melanoma model |
|
Lança T. et al, Journal of Immunology. (2013)
| Research | NA | C57BL/6 (B6) mice. B6.TCRd-/-, B6.Ccl2-/-, B6.Ccr2-/- Transplantable B16
melanoma model was used to profile chemokines in tumor lesions and assess their impact on γδ TIL recruitment in vivo. | | Cytotoxic γδ T cells infiltrate B16 lesions and delay tumor growth in vivo. B16 lesions in TCRd-deficient mice would accumulate chemokines normally consumed by γδ T cells during tumor infiltration, the CCR2 ligands: CCL2 and CCL12 were significantly overexpressed in TCRd-deficient mice. Human Vδ1 T cells (but not Vδ2) express CCR2 and migrate toward CCL2 in vitro. |
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Kunzmann V. et al, J Immunother. (2012)
| Clinical | n. 21 Patients with metastatic renal cancer, metastatic MM or AML were enrolled to receive zoledronic acid plus IL-2 with 58 treatment cycles being administered. | NA | | All patients showed an expansion in circulating γδ T cells in vivo after zoledronate and low-dose IL-2. Quantitative analysis of cytokine serum levels demonstrated that in vivo activation of γδ T lymphocytes by zoledronate plus IL-2 induced a significant increase in the proinflammatory cytokine IFN- γ. Serum VEGF levels negatively correlated with the clinical benefit. |
|
| Nicol AJ et al. British Journal of Cancer. (2011) | Clinical | Phase I trial
metastatic cancer
patients (n=18)
(n=7 melanoma).
γδ T cells were expanded ex vivo and adoptively transferred in combination with zoledronate administration | NA | NA | (i) Combination therapy
with Vγ9Vδ2 T cells and zoledronate
is well tolerated.
(ii) Better results in patients not pretreated with zoledronate.
Γδ T cells had an activated effector memory phenotype, expressed chemokine receptors predictive of Vg9Vd2 homing to peripheral tissues and were cytotoxic in vitro against tumour targets, but most patients progressed despite therapy.
(iii) the percentage of Tregs in the blood correlated with poor γδ T cells expansion |
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