Current Trends in Cancer Immunotherapy
Abstract
:1. Introduction
2. Cancer Immunity
3. Cytokine Therapy
4. Monoclonal Antibodies
Immune Checkpoint Inhibitors
5. Vaccines
5.1. Peptide-Based Therapeutic Vaccines
5.2. Therapeutic Vaccines Based on Tumor Cells
5.3. Therapeutic Vaccines Based on Dendritic Cells
5.4. Therapeutic Vaccines Based on Extracellular Vesicles
6. Oncolytic Viruses
7. CAR T-Cell Therapy
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Inhibitor Type | Drug | Cancer Type | Mechanism of Action | References |
---|---|---|---|---|
PD-1 inhibitors | Pembrolizumab | Melanoma; Hodgkin lymphoma; hepatocellular cancer (HCC); renal cell carcinoma (RCC); Head and neck squamous cell carcinoma (HNSCC); non-small-cell lung cancer (NSCLC) | A humanized IgG4 monoclonal kappa-antibody that targets the PD-1 membrane protein on the surface of T-cells, blocking it. PD-1 plays a role in the negative regulation of the immune system, preventing the activation of T-lymphocytes. | NCT02362594 NCT02362997 NCT02453594 NCT02684292 NCT03062358 NCT03142334 NCT03040999 NCT02504372 NCT02578680 NCT02775435 |
Nivolumab | Melanoma; Non-Hodgkin lymphoma; Metastatic clear cell renal carcinoma; Head and neck cancer; Metastatic colorectal cancer; NSCLC | NCT01721772 NCT01844505 NCT03068455 NCT02181738 NCT03366272 NCT01668784 NCT03342352 NCT02060188 NCT02041533 | ||
PD-L1 inhibitors | Durvalumab | Recurrent squamous cell lung cancer; Squamous cell lung carcinoma; Urothelial cancer; NSCLC | It is aimed at blocking the membrane protein PD-L1, which is a ligand for the PD-1 receptor. PD-L1 can be expressed on the cell surface of a tumor cell. When the PD-1: PD-L1 complex is formed, the T-cell receptor (TCR)-mediated positive signal is inhibited, which leads to a decrease in the activity and proliferation of T-lymphocytes. | NCT02766335 NCT02154490 NCT02516241 NCT03003962 NCT01693562 NCT03164616 |
Avelumab | RCC; Gastric and gastroesophageal junction; Urothelial cancer; NSCLC | NCT02684006 NCT02625623 NCT02603432 NCT02576574 | ||
Atezolizumab | RCC; Bladder cancer; Urothelial carcinoma; Prostatic neoplasms; NSCLC | NCT03024996 NCT02302807 NCT02807636 NCT03016312 NCT03191786 NCT03456063 | ||
CTLA-4 inhibitors | Ipilimumab | Metastatic melanoma; Gastric cancer; NSCLC | It is aimed at blocking the receptor protein CTLA-4, which is a homologue of CD28 on the surface of the T-lymphocyte, exerting an inhibitory effect on it. When T-lymphocytes interact with antigen presenting cells (APC), CTLA-4 prevents the activation of T-cells, because it has a higher affinity for the costimulatory domains CD80 and CD86 compared to the CD28 receptor. | NCT03445533 NCT02872116 NCT03351361 NCT03469960 |
NKG2A inhibitors | Monalizumab | Recurrent or metastatic HNSCC; NSCLC | It is aimed at blocking the NKG2A/CD94 receptors found in NK cells. Tumor cells use HLA-E protein molecules to bind to NKG2A, thereby exerting an inhibitory effect on the cytotoxic activity of NK cells. | NCT02643550 NCT03822351 NCT03833440 |
CARs Generations | Domains | Efficiency, (%) | Cancer Type | References |
---|---|---|---|---|
I | scFv; CD3ζ | Absent | Ovarian cancer | [202] |
II | scFv; CD28; CD3ζ | CR (11.5), PR (46), CRS (100) | Multiple myeloma | NCT02215967 |
scFv; CD28; CD3z | CR (83), CRS (85), ICANS (43), median OS 12.9 months | Chemotherapy resistant or refractory ALL | NCT01044069 | |
scFv; 4-1BB; CD3ζ | CR (69), no response (31), CRS (94), ICANS (40), median OS 19.1 months | NCT01029366 NCT02030847 | ||
III | scFv; CD28; 4-1BB; CD3z | CR (40), CRS (20), median OS 6 months | B-cell lymphoma or leukemia | NCT02132624 |
scFv; CD28; OX40; CD3ζ/CD3z, iCasp9 | NR | Neuroblastoma | NCT01822652 | |
scFv; CD28; OX40; CD3z | Neuroblastoma, Osteosarcoma | NCT01953900 | ||
IV | scFv; CD28; NFAT promoter; CD3ζ/CD3z | NR | Metastatic melanoma | NCT01236573 |
scFv; CD28; CD27; CD3z; 2A; iCasp9 | PCNSL | NCT03125577 |
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Filin, I.Y.; Solovyeva, V.V.; Kitaeva, K.V.; Rutland, C.S.; Rizvanov, A.A. Current Trends in Cancer Immunotherapy. Biomedicines 2020, 8, 621. https://doi.org/10.3390/biomedicines8120621
Filin IY, Solovyeva VV, Kitaeva KV, Rutland CS, Rizvanov AA. Current Trends in Cancer Immunotherapy. Biomedicines. 2020; 8(12):621. https://doi.org/10.3390/biomedicines8120621
Chicago/Turabian StyleFilin, Ivan Y., Valeriya V. Solovyeva, Kristina V. Kitaeva, Catrin S. Rutland, and Albert A. Rizvanov. 2020. "Current Trends in Cancer Immunotherapy" Biomedicines 8, no. 12: 621. https://doi.org/10.3390/biomedicines8120621