2. Academic Validation
  3. Novel anti-LAG-3 antibody LBL-007 with anti-PD-1 blockade enhances antitumor immunity by promoting T cell-induced apoptosis

Novel anti-LAG-3 antibody LBL-007 with anti-PD-1 blockade enhances antitumor immunity by promoting T cell-induced apoptosis

  • Sci Rep. 2025 Oct 27;15(1):37515. doi: 10.1038/s41598-025-21400-z.
Kewei Qin # 1 2,  Huinan Zhou # 3,  Xiaojie Yu 1,  Jianfei Liu 1 2,  Chenglin Wu 1 2,  Chen Zhang 4,  Lijun Zhou 5 6 7
Affiliations

Affiliations

  • 1 Central Laboratory, The Sixth Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, 100048, China.
  • 2 Senior Department of Otolaryngology Head and Neck Surgery, The Sixth Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, 100048, China.
  • 3 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • 4 The Fifth Clinical Medical College of Anhui Medical University, Hefei, 230032, Anhui, China.
  • 5 Central Laboratory, The Sixth Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, 100048, China. hzzhoulj@126.com.
  • 6 Senior Department of Otolaryngology Head and Neck Surgery, The Sixth Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, 100048, China. hzzhoulj@126.com.
  • 7 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China. hzzhoulj@126.com.
  • # Contributed equally.
PMID: 41145675 DOI: 10.1038/s41598-025-21400-z
Abstract

Immune checkpoint combination therapy, particularly dual LAG-3/PD-1 blockade, demonstrates superior clinical efficacy over monotherapy in cancers like melanoma, yet its mechanistic synergy requires further validation. In this study, we established a cell co-culture model by co-culturing LAG-3+PD-1+ Jurkat cells induced by phytohemagglutinin (PHA) and human tumor cells with high expression of LAG-3 and PD-1 major ligands to characterize the combination effect of LBL-007 with anti-PD-1 antibodies and the mechanism of action in Cancer Immunotherapy. The results showed that the combination of LBL-007 and anti-PD-1 antibodies in the cell co-culture model enhanced the ability of activated Jurkat cells to kill tumor cells compared with monotherapy. Furthermore, this combination also inhibited the Apoptosis of Jurkat cells and promoted IL-2, IL-10, and TNF secretion from Jurkat cells. Tumor cell death via Apoptosis induced by activated Jurkat cells was observed, which was enhanced by combined LBL-007 and anti-PD-1 antibody treatment. The combination of LBL-007 and anti-PD-1 antibodies delayed tumor growth and promoted tumor cell Apoptosis compared with monotherapy in human LAG-3 transgenic mice subjected to transplantation with colorectal tumor cells. Taken together, the combination of LBL-007 and anti-PD-1 antibodies plays an enhanced antitumor role by improving T cell viability and activity as well as by promoting T cell-induced Apoptosis, thereby suggesting this combination as a potential effective strategy for Cancer Immunotherapy.

Keywords

Antibody; Apoptosis; Combination blockage; Immunotherapy; LAG-3.

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