A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets
Abstract
:1. Introduction
2. Materials and Methods
2.1. Eligibility Criteria
2.2. Exclusion Criteria
2.3. Data Sources and Search Strategy
2.4. Record Screening Process
2.5. Synthesis of Results
3. Results
3.1. Programmed Cell Death-1 (PD-1)
3.1.1. PD-1 Expression on Normal T Cells
3.1.2. PD-1 Expression on HBV-Specific T Cells
3.1.3. Blocking the PD-1/PD-L1 Pathway in the Treatment of HBV Infection
3.2. Cytotoxic T Lymphocyte Antigen-4 (CTLA-4)
3.2.1. CTLA-4 Expression on Normal T Cells
3.2.2. CTLA-4 Expression on HBV-Specific T Cells
3.2.3. Blocking CTLA-4 in the Treatment of HBV Infection
3.3. T Cell Immunoglobulin and Mucin Structural Domain-3 (Tim-3)
3.3.1. Tim-3 Expression on Normal T Cells
3.3.2. Tim-3 Expression on HBV-Specific T Cells
3.3.3. The Promise of Blocking Tim-3/Tim-3L Pathway in the Treatment of HBV Infection
3.4. Lymphocyte Activation Gene 3 (LAG3)
3.4.1. LAG3 Expression on Normal T Cells
3.4.2. LAG3 Expression on HBV-Specific T Cells
3.4.3. The Promise of Blocking LAG3 in the Treatment of HBV Infection
3.5. CD244/2B4 (SLAMF4)
3.5.1. CD244/2B4 Expressed on Normal T Cells
3.5.2. CD244/2B4 Expression on HBV-Specific T Cells
3.5.3. The Promise of Blocking CD244/2B4 in the Treatment of HBV Infection
3.6. CD160
3.6.1. CD160 Expression on Normal T Cells
3.6.2. CD160 Expression on HBV-Specific T Cells
3.6.3. The Promise of Blocking CD160 in the Treatment of HBV Infection
3.7. B and T Lymphocyte Attenuator (BTLA)
3.8. T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT)
4. Conclusions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Immune Checkpoint Pathway | NCT Number | Phase | Study Start Date | Status | Inclusion Criteria | Mechanism | Drug | Primary Outcome Measures | Results | Locations |
---|---|---|---|---|---|---|---|---|---|---|
PD-1/PD-L | NCT04638439 | Phase 2 | December 2021 | Recruiting | CHB patients; HBsAg < 1500 IU/mL; HBV DNA (−) | Anti-PD-1 | P1101 Nivolumab Entecavir | Safety | N/A | Taiwan, China |
NCT05769816 | Phase 4 | June 2023 | Not yet recruiting | CHB patients | Anti-PD-1 | Anti-PD-1 antibody NAs | Serum HBsAg level | N/A | Chongqing, China | |
NCT05771402 | Phase 4 | June 2023 | Not yet recruiting | CHB patients | Anti-PD-1 | Anti-PD-1 antibody NAs Peg-IFNα | Serum HBsAg level | N/A | Chongqing, China | |
NCT05275023 | Phase 2 | June 2022 | Active, not recruiting | CHB patients; LSM ≤ 9 KPa/ metavir F0-F2 | Anti-PD-1 | JNJ-73763989 PD-1 Inhibitor NAs | HBsAg seroclearance | N/A | Toronto, Canada | |
NCT04133259 | Phase 2 | December 2019 | Unknown | CHB patients; HBsAg > 100 IU/mL; HBV DNA < 2000 IU/mL | Anti-PD-1 | HLX10 NAs | Levels of HBsAg decline | N/A | Taiwan, China | |
NCT05242445 | Phase 1 | April 2022 | Active, not recruiting | CHB patients; LSM ≤ 9 KPa/ metavir F0-F2 | Anti-PD-1 | Cetrelimab (JNJ-63723283) Placebo | Pharmacokinetics, Pharmacodynamics, and safety of single doses of Cetrelimab (JNJ 63723283), | N/A | Belgium; France; Germany; Poland; Spain | |
NCT04294498 | Phase 2 | November 2020 | Recruiting | HBeAg (−); HBsAg (+); HBV DNA ≥ 2000 IU/mL; Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy (Advanced Hepatocellular Carcinoma) | Anti-PD-1 | Durvalumab | The rate of HBV reactivation during durvalumab treatment | N/A | Taiwan, China | |
NCT04044651 | Phase 3 Phase 2 | October 2019 | Withdrawn | HBsAg (+); BCLC (C stage) | Anti-PD-1 | Nivolumab Lenvatinib | Overall survival (OS). Time frame: 18 months | N/A | Guangdong, China | |
NCT04465890 | Phase 2 | July 2020 | Recruiting | HBV DNA (−); HBeAg (−); HBsAg ≤ 10,000 IU/mL | Anti-PD-L1 | PD-L1 Antibody (ASC22) | Levels of HBsAg decline | N/A | Beijing, China | |
NCT04225715 | Phase 2 | July 2020 | Recruiting | HBsAg (+) ≥ 6 months; HBV DNA below the lower LLOQ or <20 IU/mL for >6 months | Anti-PD-L1 | NUCs CpAM (RO7049389) TLR7 (RO7020531) siRNA (RO7445482) PEG-IFN PD-L1 LNA (RO7191863) | HBsAg seroclearance | N/A | 54 study locations including United States, Canada et al. | |
NCT04680598 | N/A | December 2020 | Recruiting | HBsAg (+); HCC (for EASL) | Anti-PD-1/anti-PD-L1 | ICI (including PD-1 inhibitor or PD-L1 inhibitor); NAs | HBV reactivation rate | N/A | Guangdong, China | |
NCT03419481 | Phase 2 | April 2018 | Recruiting | HBsAg (+); HBV DNA < 100 IU/mL; HCC (for AASLD) | Anti-PD-L1 | pembrolizumab | Response rate (RR) according to RECIST1.1. Time frame: 2 years | N/A | Hong Kong, China | |
LAG3 | NCT00354861 | Phase 1 | May 2005 | Completed | Healthy | hLAG-3Ig | IMP321 (AG-3) | Safety and tolerability profiles. Time frame: 3 months | IMP321 was very well tolerated | Paris, France |
PubMed | Search query: (“Hepatitis B”MeSH Terms OR “HBV”All Fields) AND (“Costimulatory and Inhibitory T-Cell Receptors”MeSH Terms OR (“inhibitory”All Fields AND (“cell cycle checkpoints”MeSH Terms OR (“cell”All Fields AND “cycle”All Fields AND “checkpoints”All Fields) OR “cell cycle checkpoints”All Fields OR “checkpoint”All Fields OR “checkpoints”All Fields)) OR ((“immune”All Fields OR “immuned”All Fields OR “immunes”All Fields OR “immunisation”All Fields OR “vaccination”MeSH Terms OR “vaccination”All Fields OR “immunization”All Fields OR “immunization”MeSH Terms OR “immunisations”All Fields OR “immunizations”All Fields OR “immunise”All Fields OR “immunised”All Fields OR “immuniser”All Fields OR “immunisers”All Fields OR “immunising”All Fields OR “immunities”All Fields OR “immunity”MeSH Terms OR “immunity”All Fields OR “immunization s”All Fields OR “immunize”All Fields OR “immunized”All Fields OR “immunizer”All Fields OR “immunizers”All Fields OR “immunizes”All Fields OR “immunizing”All Fields) AND (“cell cycle checkpoints”MeSH Terms OR (“cell”All Fields AND “cycle”All Fields AND “checkpoints”All Fields) OR “cell cycle checkpoints”All Fields OR “checkpoint”All Fields OR “checkpoints”All Fields)) OR (“PD-1”All Fields OR (“ctla 4 antigen”MeSH Terms OR (“ctla 4”All Fields AND “antigen”All Fields) OR “ctla 4 antigen”All Fields OR “ctla 4”All Fields) OR “LAG3”All Fields OR “Tim-3”All Fields OR “cd244”All Fields OR “CD160”All Fields OR “TIGIT”All Fields OR “BTLA”All Fields)) AND (“T-Lymphocytes”MeSH Terms OR (“T-Lymphocytes”MeSH Terms OR “T-Lymphocytes”All Fields OR “t cell”All Fields)) |
Results: 396 | |
Web of Science | ((hepatitis B (Topic) or HBV (Topic) and Preprint Citation Index (Exclude—Database)) AND inhibitory receptors (Topic) or inhibitory checkpoints (Topic) or immunization checkpoints (Topic) and Preprint Citation Index (Exclude—Database)) AND T lymphocyte (Topic) or T cell (Topic) and Preprint Citation Index (Exclude—Database) and Preprint Citation Index (Exclude—Database) |
Result: 492 | |
Scopus | (((ALL(hepatitis B) OR ALL(HBV))) AND ((ALL(inhibitory AND receptors) OR ALL(inhibitory AND checkpoints) OR ALL(immunization AND checkpoints))) AND ((ALL(T lymphocyte) OR ALL(T cell))) AND (LIMIT-TO (LANGUAGE,”English”)) AND (LIMIT-TO (DOCTYPE,”ar”)) AND (LIMIT-TO (EXACTKEYWORD,”Hepatitis B”) OR LIMIT-TO (EXACTKEYWORD,”T-Lymphocytes”) OR LIMIT-TO (EXACTKEYWORD,”Hepatitis B Virus”) OR LIMIT-TO (EXACTKEYWORD,”T Lymphocyte”))) |
Results: 3310 |
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Zhou, D.; Liu, L.; Liu, J.; Li, H.; Zhang, J.; Cao, Z. A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets. J. Clin. Med. 2024, 13, 1210. https://doi.org/10.3390/jcm13051210
Zhou D, Liu L, Liu J, Li H, Zhang J, Cao Z. A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets. Journal of Clinical Medicine. 2024; 13(5):1210. https://doi.org/10.3390/jcm13051210
Chicago/Turabian StyleZhou, Daqiong, Lili Liu, Jiangyu Liu, Hong Li, Jing Zhang, and Zhenhuan Cao. 2024. "A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets" Journal of Clinical Medicine 13, no. 5: 1210. https://doi.org/10.3390/jcm13051210
APA StyleZhou, D., Liu, L., Liu, J., Li, H., Zhang, J., & Cao, Z. (2024). A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets. Journal of Clinical Medicine, 13(5), 1210. https://doi.org/10.3390/jcm13051210