Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimization Article Swipe
Kanta Hori
,
Shuhei Yamada
,
Kenji Murata
,
Haruka Miyata
,
Yuka Mizue
,
Aiko Murai
,
Tomoyuki Minowa
,
Kenta Sasaki
,
Naoki Shijubou
,
Terufumi Kubo
,
Rena Morita
,
Serina Tokita
,
Takayuki Kanaseki
,
Tomohide Tsukahara
,
Takashige Abe
,
Nobuo Shinohara
,
Yoshihiko Hirohashi
,
Toshihiko Torigoe
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1080/21645515.2024.2414542
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1080/21645515.2024.2414542
Adoptive T cell therapy, using T cell receptor-engineered T (TCR-T) cells and chimeric antigen receptor T (CAR-T) cells, is a potent immunotherapy option. Bladder cancer is a prevalent urological malignancy, particularly in cases of muscle invasion and metastasis, for which systemic therapy is crucial. Immunotherapy utilizing immune checkpoint blockade has been approved for bladder cancer treatment. The antitumor effect of an immune checkpoint blockade based on cytotoxic T cells (CTLs) and the patient's immune status is essential. The chemotherapeutic drug cisplatin (CDDP) is a key drug in bladder cancer treatment. However, it has been shown to suppress T cells, making combination therapy with CDDP and immunotherapy difficult. To address this, we developed TCR-T cells specific for bladder cancer cells. In previous studies, we found that the tumor-associated antigen CLSPN is overexpressed in CDDP-resistant bladder cancer cells and that the antigenic peptide HLA-A*02:01/CLSPN1254-1262, encoded by CLSPN, could be targeted by a CTL clone. The TCR was cloned from the HLA-A*02:01/CLSPN1254-1262 specific CTL clone yc3. We also designed a codon-optimized TCR sequence using GeneArt® GeneOptimizer® (Opt TCR) and compared the TCR-T cells using the original TCR sequence (Ori TCR-T cells) and the codon-optimized TCR sequence (Opt TCR-T cells). Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN1254-1262 specific Opt TCR-T cells are promising candidates for CDDP combination therapy.
Related Topics
Concepts
T-cell receptor
Immunotherapy
Cytotoxic T cell
Antigen
Cancer research
Biology
CTL*
Adoptive cell transfer
Immunology
clone (Java method)
T cell
Cancer immunotherapy
Immune system
CD8
Genetics
In vitro
Biochemistry
DNA
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1080/21645515.2024.2414542
- OA Status
- gold
- Cited By
- 1
- References
- 39
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4404363866
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4404363866Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1080/21645515.2024.2414542Digital Object Identifier
- Title
-
Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimizationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-11-13Full publication date if available
- Authors
-
Kanta Hori, Shuhei Yamada, Kenji Murata, Haruka Miyata, Yuka Mizue, Aiko Murai, Tomoyuki Minowa, Kenta Sasaki, Naoki Shijubou, Terufumi Kubo, Rena Morita, Serina Tokita, Takayuki Kanaseki, Tomohide Tsukahara, Takashige Abe, Nobuo Shinohara, Yoshihiko Hirohashi, Toshihiko TorigoeList of authors in order
- Landing page
-
https://doi.org/10.1080/21645515.2024.2414542Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1080/21645515.2024.2414542Direct OA link when available
- Concepts
-
T-cell receptor, Immunotherapy, Cytotoxic T cell, Antigen, Cancer research, Biology, CTL*, Adoptive cell transfer, Immunology, clone (Java method), T cell, Cancer immunotherapy, Immune system, CD8, Genetics, In vitro, Biochemistry, DNATop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1Per-year citation counts (last 5 years)
- References (count)
-
39Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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