Triggering of lymphocytes by CD28, 4-1BB, and PD-1 checkpoints to enhance the immune response capacities Article Swipe
Elina Kaviani
,
Ahmad Hosseini
,
Elham Mahmoudi Maymand
,
Mani Ramzi
,
Abbas Ghaderi
,
Amin Ramezani
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0275777
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0275777
Tumor infiltrating lymphocytes (TILs) usually become exhausted and dysfunctional owing to chronic contact with tumor cells and overexpression of multiple inhibitor receptors. Activation of TILs by targeting the inhibitory and stimulatory checkpoints has emerged as one of the most promising immunotherapy prospectively. We investigated whether triggering of CD28, 4-1BB, and PD-1 checkpoints simultaneously or alone could enhance the immune response capacity of lymphocytes. In this regard, anti-PD-1, CD80-Fc, and 4-1BBL-Fc proteins were designed and produced in CHO-K1 cells as an expression host. Following confirmation of the Fc fusion proteins’ ability to bind to native targets expressed on engineered CHO-K1 cells (CHO-K1/hPD-1, CHO-K1/hCD28, CHO-K1/hCTLA4, and CHO-K1/h4-1BB), the effects of each protein, on its own and in various combinations, were assessed in vitro on T cell proliferation, cytotoxicity, and cytokines secretion using the Mixed lymphocyte reaction (MLR) assay, 7-AAD/CFSE cell-mediated cytotoxicity assay, and a LEGENDplex™ Human Th Cytokine Panel, respectively. MLR results demonstrated that T cell proliferation in the presence of the combinations of anti-PD-1/CD80-Fc, CD80-Fc/4-1BBL-Fc, and anti-PD-1/CD80-Fc/4-1BBL-Fc proteins was significantly higher than in the untreated condition (1.83-, 1.91-, and 2.02-fold respectively). Furthermore, anti-PD-1 (17%), 4-1BBL-Fc (19.2%), anti-PD-1/CD80-Fc (18.6%), anti-PD-1/4-1BBL-Fc (21%), CD80-Fc/4-1BBL-Fc (18.5%), and anti-PD-1/CD80-Fc/4-1BBL-Fc (17.3%) significantly enhanced cytotoxicity activity compared to untreated condition (7.8%). However, concerning the cytokine production, CD80-Fc and 4-1BBL-Fc alone or in combination significantly increased the secretion of IFN‐γ, TNF-α, and IL-2 compared with the untreated conditions. In conclusion, this research establishes that the various combinations of produced anti-PD-1, CD80-Fc, and 4-1BBL-Fc proteins can noticeably induce the immune response in vitro . Each of these combinations may be effective in killing or destroying cancer cells depending on the type and stage of cancer.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0275777
- OA Status
- gold
- Cited By
- 9
- References
- 39
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4311589761
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4311589761Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1371/journal.pone.0275777Digital Object Identifier
- Title
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Triggering of lymphocytes by CD28, 4-1BB, and PD-1 checkpoints to enhance the immune response capacitiesWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-12-08Full publication date if available
- Authors
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Elina Kaviani, Ahmad Hosseini, Elham Mahmoudi Maymand, Mani Ramzi, Abbas Ghaderi, Amin RamezaniList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0275777Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1371/journal.pone.0275777Direct OA link when available
- Concepts
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CD80, CD28, Immune system, Molecular biology, Biology, Cytokine, Cytotoxicity, CD86, T cell, Immunology, Chemistry, Cancer research, Cell biology, In vitro, Cytotoxic T cell, CD40, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 4, 2024: 1, 2023: 4Per-year citation counts (last 5 years)
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39Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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