Li Yating
Email Address
phsliy@nus.edu.sg
Organizational Units
YONG LOO LIN SCH OF MEDICINE
faculty
PHYSIOLOGY
dept
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Publication Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells(Frontiers Media S.A., 2019) Rajendran, S.; Li, Y.; Ngoh, E.; Wong, H.Y.; Cheng, M.S.; Wang, C.-I.; Schwarz, H.; PHYSIOLOGYHodgkin Lymphoma (HL) is a malignancy that frequently affects young adults. Although, there are effective treatments not every patient responds, necessitating the development of novel therapeutic approaches, especially for relapsed and refractory cases. The two TNF receptor family members CD30 and CD137 are expressed on Hodgkin and Reed Sternberg (HRS) cells, the malignant cells in HL. We found that this co-expression is specific for HRS cells. Based on this discovery we developed a bispecific antibody that binds preferentially to the CD30, CD137-double positive HRS cells. The CD30, CD137 bispecific antibody gets internalized into HRS cells opening up the possibility to use it as a carrier for a toxin. This antibody also induces antibody-dependent, cell-mediated cytotoxicity in CD30, CD137-double positive HRS cells. The enhances specificity of the CD30, CD137 bispecific antibody to HRS cells makes it a promising candidate for development as a novel HL treatment. © Copyright © 2019 Rajendran, Li, Ngoh, Wong, Cheng, Wang and Schwarz.Publication Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma is safe and confers clinical benefit(SPRINGER, 2021-10-18) Nickles, Emily; Dharmadhikari, Bhushan; Li, Yating; Walsh, Robert J; Koh, Liang Piu; Poon, Michelle; Tan, Lip Kun; Wang, Ling-Zhi; Ang, Yvonne; Asokumaran, Yugarajah; Chong, Wan Qin; Huang, Yiqing; Loh, Kwok Seng; Tay, Joshua; Soo, Ross; Koh, Mickey; Ho, Liam Pock; Chan, Marieta; Niam, Madelaine; Soh, Melissa; Luah, Yen Hoon; Lim, Chwee Ming; Kaliaperumal, Nivashini; Au, Veonice B; Talib, Najwa Binte Said Nasir; Sng, Reina; Connolly, John E; Goh, Boon Cher; Schwarz, Herbert; Assoc Prof Herbert Schwarz; MEDICINE; PHYSIOLOGY; MICROBIOLOGY AND IMMUNOLOGY; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); CANCER SCIENCE INSTITUTE OF SINGAPORE; BIOMED INST FOR GLOBAL HEALTH RES & TECH; OTOLARYNGOLOGY; DUKE-NUS MEDICAL SCHOOL; PATHOLOGYIntroduction: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), and provides a target for a dendritic cell (DC) vaccine. CD137 ligand (CD137L) expressed on antigen presenting cells, costimulates CD137-expressing T cells, and reverse CD137L signaling differentiates monocytes to CD137L-DC, a type of DC, which is more potent than classical DC in stimulating T cells. Methods: In this phase I study, patients with locally recurrent or metastatic NPC were administered CD137L-DC pulsed with EBV antigens (CD137L-DC-EBV-VAX). Results: Of the 12 patients treated, 9 received full 7 vaccine doses with a mean administered cell count of 23.9 × 106 per dose. Treatment was well tolerated with only 4 cases of grade 1 related adverse events. A partial response was obtained in 1 patient, and 4 patients are still benefitting from a progression free survival (PFS) of currently 2–3 years. The mean pre-treatment neutrophil: lymphocyte ratio was 3.4 and a value of less than 3 was associated with prolonged median PFS. Progressors were characterized by a high frequency of naïve T cells but a low frequency of CD8+ effector T cells while patients with a clinical benefit (CB) had a high frequency of memory T cells. Patients with CB had lower plasma EBV DNA levels, and a reduction after vaccination. Conclusion: CD137L-DC-EBV-VAX was well tolerated. The use of CD137L-DC-EBV-VAX is demonstrated to be safe. Consistent results were obtained from all 12 patients, indicating that CD137L-DC-EBV-VAX induces an anti-EBV and anti-NPC immune response, and warranting further studies in patients post effective chemotherapy. Precis. The first clinical testing of CD137L-DC, a new type of monocyte-derived DC, finds that CD137L-DC are safe, and that they can induce an immune response against Epstein-Barr virus-associated nasopharyngeal carcinoma that leads to tumor regression or prevents tumor progression.Publication Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma (NPC).(LIPPINCOTT WILLIAMS & WILKINS, 2020-05-20) Walsh, Robert John; Nickles, Emily Pauline; Li, Yating; Dharmadhikari, Bhushan; Koh, Mickey; Ho, Liam Pock; Chan, Marieta; Koh, Liang Piu; Poon, Michelle Li Mei; Tan, Lip Kun; Huang, Yiqing; Ang, Yvonne Li'en; Chong, Wan Qin; Asokumaran, Yugarajah; Loh, Kwok Seng; Soo, Ross A; Lim, Chwee Ming; Schwarz, Herbert; Goh, Boon Cher; Assoc Prof Herbert Schwarz; MEDICINE; PHYSIOLOGY; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); CANCER SCIENCE INSTITUTE OF SINGAPORE; OTOLARYNGOLOGY; DUKE-NUS MEDICAL SCHOOL; PATHOLOGYPublication Epstein–Barr virus-encoded LMP1 induces ectopic CD137 expression on Hodgkin and Reed–Sternberg cells via the PI3K-AKT-mTOR pathway(2019-01-01) SNEHA PRIYA ARAVINTH; Rajendran, S; Li, Y; Wu, M; Yi Wong, AH; Schwarz, H; Assoc Prof Schwarz, Herbert; MEDICINE; PHYSIOLOGY© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. CD137 is a potent co-stimulatory molecule on activated T cells, and its ligand (CD137L) is expressed on antigen presenting cells (APC). Ectopic expression of CD137 has been identified on Hodgkin Reed–Sternberg (HRS) cells, the malignant cells in Hodgkin Lymphoma (HL), and CD137 on HRS cells was found to support growth of HRS cells and escape from immune surveillance. HRS cells are mostly derived from B cells, which poses the question of how B cells acquire ectopic CD137 expression during the transformation process. HL is associated with Epstein–Barr virus (EBV) infection. We show that the EBV latent membrane protein 1 (LMP1) induces expression of CD137 in HRS cell lines. In a HL tissue microarray, 96% of the CD137-positive HL cases stained positive for LMP1. LMP1 utilizes the PI3K-AKT-mTOR pathway for inducing CD137 expression. These findings support the role of EBV in HL pathogenesis.