DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jeon, Seung Hyuck | ko |
dc.contributor.author | You, Gihoon | ko |
dc.contributor.author | Park, Junsik | ko |
dc.contributor.author | Chung, Youseung | ko |
dc.contributor.author | Park, Kyungjin | ko |
dc.contributor.author | Kim, Hyunjoo | ko |
dc.contributor.author | Jeon, Jaehyoung | ko |
dc.contributor.author | Kim, Youngkwang | ko |
dc.contributor.author | Son, Woo-Chan | ko |
dc.contributor.author | Jeong, Da Som | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Lee, Jung-Yun | ko |
dc.contributor.author | Han, Dai Hoon | ko |
dc.contributor.author | Jung, Jaeho | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.date.accessioned | 2024-08-23T01:00:12Z | - |
dc.date.available | 2024-08-23T01:00:12Z | - |
dc.date.created | 2024-08-23 | - |
dc.date.issued | 2024-06 | - |
dc.identifier.citation | Clinical Cancer Research, pp.OF1 - OF12 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | http://hdl.handle.net/10203/322395 | - |
dc.description.abstract | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti–4-1BB×PDL1 bispecific antibody—ABL503 (also known as TJ-L14B)—was designed to simultaneously target PDL1 and 4-1BB and demonstrated strong antitumor T-cell responses without considerable toxicity. In this study, we investigated the mechanisms by which the combination of ABL503 and anti-PD1 blockade affected the reinvigoration of exhausted tumor-infiltrating CD8+ T cells (CD8+ TIL) and antitumor efficacy.</jats:p> </jats:sec> <jats:sec> <jats:title>Experimental Design:</jats:title> <jats:p>Single-cell suspensions of hepatocellular carcinoma and ovarian cancer tissues from treatment-naïve patients were used for immunophenotyping of CD8+ TILs and in vitro functional assays. Humanized hPD1/hPDL1/h4-1BB triple–knock-in mice were used to evaluate the effects of ABL503 and anti-PD1 blockade in vivo.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>We observed that ABL503 successfully restored the functions of 4-1BB+ exhausted CD8+ TILs, which were enriched for tumor-specific T cells but unresponsive to anti-PD1 blockade. Importantly, compared with anti-PD1 blockade alone, the combination of ABL503 and anti-PD1 blockade further enhanced the functional restoration of human CD8+ TILs in vitro. Consistently, the combination of ABL503 with anti-PD1 in vivo significantly alleviated tumor growth and induced enhanced infiltration and activation of CD8+ TILs.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>ABL503, a PDL1 and 4-1BB dual-targeting bispecific antibody, elicits pronounced additive tumor growth inhibition, with increased infiltration and functionality of exhausted CD8+ T cells, which in turn enhances the anticancer effects of anti-PD1 blockade. These promising findings suggest that ABL503 (TJ-L14B) in combination with PD1 inhibitors will likely further enhance therapeutic benefit in clinical trials.</jats:p> </jats:sec> | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research (AACR) | - |
dc.title | Anti–4-1BB×PDL1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD1 Blockade | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.citation.beginningpage | OF1 | - |
dc.citation.endingpage | OF12 | - |
dc.citation.publicationname | Clinical Cancer Research | - |
dc.identifier.doi | 10.1158/1078-0432.ccr-23-2864 | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.nonIdAuthor | You, Gihoon | - |
dc.contributor.nonIdAuthor | Park, Junsik | - |
dc.contributor.nonIdAuthor | Park, Kyungjin | - |
dc.contributor.nonIdAuthor | Kim, Hyunjoo | - |
dc.contributor.nonIdAuthor | Jeon, Jaehyoung | - |
dc.contributor.nonIdAuthor | Kim, Youngkwang | - |
dc.contributor.nonIdAuthor | Son, Woo-Chan | - |
dc.contributor.nonIdAuthor | Jeong, Da Som | - |
dc.contributor.nonIdAuthor | Lee, Jung-Yun | - |
dc.contributor.nonIdAuthor | Han, Dai Hoon | - |
dc.contributor.nonIdAuthor | Jung, Jaeho | - |
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