Table 1.
Clinical trials for the treatment of HNSCC patients targeting the immune system.
| Target | NCT Number |
Status | Interventions | Phases | Enrolled Patients, n |
Period (Start Date–Completion Date) |
URL Access | Related Articles with Results |
HPV Status | Immune Dynamics Evaluation | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Intratumor Microenvironment | Peripheral Blood Cells | ||||||||||
| Inflammatory cell subsets | NCT00210470 | Completed | IRX-2 (multiple cytokines) Cyclophosphamide Indomethacin Zinc Omeprazole |
2 | 27 | 2005/07–2012/03 | https://ClinicalTrials.gov/show/NCT00210470 (accessed on 28 September 2022) | [126,127,128,129] | n.d. ** | Increased infiltration of TILs (CD3+, CD4+, CD8+ and CD20+ B cells) and CD68+ macrophages in tumor microenvironment. Peritumoral accumulation of CD4+ T cells. Predominance of intratumor CD8+ over CD4+ T cells. Higher CD20+ cells were associated with decreased tumor size. Increased survival rates associated with intratumor CD3+ and CD20+ cells. |
Decreased levels of naïve T cells (CD3+CD45RA+CCR7+), central memory T cells (CD3+CD45RA−CCR7+CD27+), B lymphocytes (CD19+CD3−CD14−) and NKT cells (CD3+CD16+CD56+). |
| p-53- expressing tumor cells | NCT00496860 | Completed | ALT-801 (humanized soluble T-cell receptor directed against the p53-derived antigen fused to IL-2) | 1 | 26 | 2007/05–2009/10 | https://ClinicalTrials.gov/show/NCT00496860 (accessed on 28 September 2022) | [130] | n.d. | n.d. ** | Increased number of IFN-γ+ cells. Elevated serum IFN-γ levels. |
| Phosphodiesterase type-5 | NCT00843635 | Completed | Tadalafil (phosphodiesterase 5 (PDE5) inhibitor) | n/a * | 35 | 2008/09–2015/04 | https://ClinicalTrials.gov/show/NCT00843635 (accessed on 28 September 2022) | [131] | n.d. | n.d. | Decrease in m-MDSC and Treg cells numbers. Significant downregulation of MDSCs and nFoxp3:cFoxp3 ratio. Increased CD8+ cell activation. |
| Intratumor reactive T-cells and endothelial cells | NCT00953849 | Completed | Celecoxib (cyclooxygenase 2 inhibitor) Calcitriol (Vitamin D) |
1|2 | 21 | 2009/11–2015/12 | https://ClinicalTrials.gov/show/NCT00953849 (accessed on 28 September 2022) | none | n.d. | Intra-tumor increased IL-2, IFN-γ, and GM-CSF and decreased IL-6 staining. | n.d. |
| Tumor cells | NCT01302834 | Unknown | cetuximab (anti-EGFR mAb) cisplatin (apoptosis-inducer via DNA crosslinking) MRT |
3 | 987 | 2011/02– | https://ClinicalTrials.gov/show/NCT01302834 (accessed on 28 September 2022) | [132] | Yes | n.d. | n.d. |
| Interleukin-6 | NCT01403064 | Terminated | ALD518 (humanized anti-IL-6 antibody) | 2 | 76 | 2011/07–2014/03 | https://ClinicalTrials.gov/show/NCT01403064 (accessed on 28 September 2022) | none | n.d. | n.d. | n.d. |
| Anti-tumor cellular immunity | NCT01468896 | Active, not recruiting | Cetuximab (anti-EGFR mAb) Edodekin alfa (recombinant IL-12) |
1|2 | 23 | 2011/11– | https://ClinicalTrials.gov/show/NCT01468896 (accessed on 28 September 2022) | none | n.d. | n.d. | n.d. |
| HPV-infected cells and tumor cells | NCT01585428 | Completed | Fludarabine (inhibitor of DNA synthesis) Cyclophosphamide (inhibitor of protein synthesis) Young TIL (Tumor Infiltrating Lymphocytes) Aldesleukin (recombinant IL-2) |
2 | 29 | 2012/04–2016/08 | https://ClinicalTrials.gov/show/NCT01585428 (accessed on 28 September 2022) | [133] | Yes | n.d. | n.d. |
| Phosphodiesterase type-5 | NCT01697800 | Completed | Tadalafil (phosphodiesterase 5 (PDE5) inhibitor) | 2 | 40 | 2012/09–2014/07 | https://ClinicalTrials.gov/show/NCT01697800 (accessed on 28 September 2022) | none | n.d. | n.d. | n.d. |
| Inflammation and pain | NCT01883908 | Terminated | Acupuncture Usual medical care for pain relief |
n/a | 4 | 2012/12–2015/02 | https://ClinicalTrials.gov/show/NCT01883908 (accessed on 28 September 2022) | none | n.d. | n.d. | n.d. |
| Innate and adaptive immunity crosstalk | NCT01984892 | Terminated | Poly-ICLC (TLR3-ligand) | 2 | 8 | 2013/11–2014/08 | https://ClinicalTrials.gov/show/NCT01984892 (accessed on 28 September 2022) | [134] | n.d. | n.d. | n.d. |
| HPV-specific T cell repertoire | NCT02002182 | Active, not recruiting | ADXS11-001/ADXS-HPV (immunobiological product from Listeria monocytogenes) | 2 | 15 | 2013/12–2023/08 | https://ClinicalTrials.gov/show/NCT02002182 (accessed on 28 September 2022) | none | Yes | n.d. | No difference between treatment and control groups on HPV-specific T cell response rate. |
| HPV-specific T and B cell repertoires | NCT02163057 | Completed | INO-3112 (plasmids encoding HPV oncoproteins delivered by electroporation system) | 1|2 | 22 | 2014/08–2017/01 | https://ClinicalTrials.gov/show/NCT02163057 (accessed on 28 September 2022) | none | Yes | Suggestive modulation of CD8+, perforin+ and FoxP3+ TILs. | n.d. |
| HPV-infected cells and tumor cells | NCT02280811 | Completed | Fludarabine (inhibitor of DNA synthesis) Cyclophosphamide (inhibitor of protein synthesis) E6 TCR (T cells genetically engineered with a TCR targeting HPV-16 E6 oncoprotein) Aldesleukin (recombinant IL-2) |
1|2 | 12 | 2014/10–2016/06 | https://ClinicalTrials.gov/show/NCT02280811 (accessed on 28 September 2022) | none | Yes | n.d. | Inconclusive results. |
| Anti-tumor cellular immunity | NCT02315066 | Completed | PF-04518600 (OX40 agonist) PF-05082566 (4-1BB agonist) |
1 | 174 | 2015/04–2020/11 | https://ClinicalTrials.gov/show/NCT02315066 (accessed on 28 September 2022) | [135] | n.d. | Upregulation of gene sets associated with anti-tumor immune response, mainly IFN-γ-related pathways. | Increased CD4+ and CD8+ T-cell clonal expansion. |
| Anti-tumor cellular immunity | NCT02521870 | Terminated | SD-101 (synthetic CpG oligonucleotide acting as TLR9 ligand) Pembrolizumab (programmed death receptor-1 (PD-1)-blocking antibody) |
1|2 | 241 | 2015/09–2020/04 | https://ClinicalTrials.gov/show/NCT02521870 (accessed on 28 September 2022) | [136] | n.d. | n.d. | n.d. |
| Lymph system | NCT03332160 | Completed | Flexitouch (pneumatic compression device) | n/a | 49 | 2018/01–2019/07 | https://ClinicalTrials.gov/show/NCT03332160 (accessed on 28 September 2022) | none | n.d. | n.d. | A slight decrease in IL-6 levels. |
| Intratumor reactive T-cells | NCT03463161 | Terminated | Pembrolizumab (programmed death receptor-1 (PD-1)-blocking antibody) Epacadostat (selective inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) |
2 | 2 | 2018/03–2018/12 | https://ClinicalTrials.gov/show/NCT03463161 (accessed on 28 September 2022) | none | Yes | n.d. | n.d. |
| Intratumor reactive T-cells | NCT03938337 | Terminated | Pembrolizumab (programmed death receptor-1 (PD-1)-blocking antibody) Abemaciclib (inhibitor of cyclin-dependent kinases (CDK)) |
2 | 1 | 2019/10–2020/04 | https://ClinicalTrials.gov/show/NCT03938337 (accessed on 28 September 2022) | none | n.d. | n.d. | n.d. |
| HPV-infected cells and tumor cells | NCT04015336 | Terminated | E7 TCR (T cells genetically engineered with a TCR targeting HPV-16 E7 oncoprotein) | 2 | 1 | 2020/06–2020/07 | https://ClinicalTrials.gov/show/NCT04015336 (accessed on 28 September 2022) | none | Yes | n.d. | n.d. |
| Intratumor reactive T-cells and NK cells | NCT04099277 | Terminated | LY3435151 (anti-CD226) Pembrolizumab (programmed death receptor-1 (PD-1)-blocking antibody) |
1 | 2 | 2019/10–2020/03 | https://ClinicalTrials.gov/show/NCT04099277 (accessed on 28 September 2022) | none | n.d. | n.d. | n.d. |
| Intratumor reactive T-cells | NCT01848834 | Completed | Pembrolizumab (programmed death receptor-1 (PD-1)-blocking antibody) | 1 | 297 | 2013/05–2020/06 | https://ClinicalTrials.gov/show/NCT01848834 (accessed on 28 September 2022) | [137,138,139,140,141] | Yes | n.d. | n.d. |
| Intratumor reactive T-cells | NCT03083873 | Completed | LN-145 (autologous TIL-mediated adoptive cell transfer therapy) recombinant IL-2 non-myeloablative (NMA) lymphodepletion |
2 | 112 | 2017/01–2022/03 | https://clinicaltrials.gov/ct2/show/NCT03083873 (accessed on 28 September 2022) | none | Yes | n.d. | n.d. |
Data source: adapted from ClinicalTrials.gov. * n/a = not applicable. ** n.d. = not described.