Research Areas of Interest:

1. Tumor vaccination

We have developed a new type of dendritic cells (DC) that are generated by a CD137 ligand (CD137L) agonist, and that proved to be more effective in vitro than conventional monocyte-derived DC. Recently, we tested these CD137L-DC that were pulsed with peptides from Epstein-Barr virus proteins, in a phase I clinical trial on patients with advanced nasopharyngeal carcinoma. CD137L-DC-EBV-VAX was safe and well tolerated, and induced a clinical benefit in 5 of 12 patients (Nickles et al., 2022, PMID: 34661709).

Currently, we are preparing the second arm of this trial where we combine CD137L-DCEBV- Vax with an anti-PD-1 antibody. In an independent project, we are constructing recombinant Adenovirus with CD137L as an adjuvant for enhancing vaccine efficacy.

2. Converting the immunosuppressive TME of solid cancers to an Immunostimulatory milieu

We are developing several switch receptors with the aim of reversing immune suppression within the tumor microenvironment (TME). One of these switch receptors is a PD1-CD137L fusion protein, consisting of the extracellular domains of PD-1 and CD137L, that binds to the immunosuppressive PDL1 within the TME, and converts it to the immunostimulatory CD137L signal. Further, we are developing anti- CD137 antibodies that are designed to deplete intratumoral regulatory T cells.

Selected Publications

1. Lee Kang Yi, Hiu Yi Wong, Qun Zeng, Man Si Cheng, Jia Le Lin, Chik Hong Kuick, Kenneth Tou En Chang, Amos Hong Pheng Loh, Herbert Schwarz. Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting. OncoImmunology, 10(1):1877459, 2021.
2. Prasad Mukul, Jia Le Lin, Gu Yue, Rashi Gupta, Paul Macary, Herbert Schwarz. No crossreactivity of anti-SARS-CoV-2 spike protein antibodies to Syncytin-1. Cellular & Molecular Immunology, Nov;18(11):2566-2568, 2021.
3. Nickles Emily, Bhushan Dharmadhikari, Li Yating, Robert J. Walsh, Liang Piu Koh, Michelle Poon, Lip Kun Tan, Ling-Zhi Wang, Yvonne Ang, Yugarajah Asokumaran, Wan Qin Chong, Yiqing Huang, Kwok Seng Loh, Joshua Tay, R. Soo, Mickey Koh, Liam Pock Ho, Marieta Chan, Madelaine Niam, Meliss Soh, Yen Hoon Luah, Chwee Ming Lim, Nivashini Kaliaperumal, Veonice B. Au, Najwa Binte Said Nasir Talib, Reina Sng, John E. Connolly, Boon Cher Goh, Herbert Schwarz. Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma is safe and confers clinical benefit. Cancer Immunology, Immunotherapy, 71(6):1531-1543, 2022.
4. Prasad Mukul, Sashigala Ponnalagu, Qun Zeng, Khang Luu, Si Min Lang, Hiu Yi Wong, Man Si Cheng, Meihui Wu, Karthik Mallilankaraman, Radoslaw Mikolaj Sobota, Yan Ting Lim, Loo Chien Wang, Chuan Keng Goh, Kai Xun Joshua Tay, Kwok Seng Loh, Cheng-I Wang, Wen-Hsien Lee, Boon Cher Goh, Chwee Ming Lim, Herbert Schwarz. Epstein-Barr Virus-Induced Ectopic CD137 Expression Helps Nasopharyngeal Carcinoma to Escape Immune Surveillance and Enables Targeting by Chimeric Antigen Receptors. Cancer Immunology, Immunotherapy, 71(11):2583-2596, 2022.
5. Sun Rui, Jia Le Lin, Man Si Cheng, Kang Yi Lee, Thilo Spruss, Christa Buechler, Herbert Schwarz. Loss of chemerin in rhabdomyosarcoma cells polarizes adjacent monocytes to an immunosuppressive phenotype. BioMedicines, 10(10):2610,