Biology subjects

Tan, G. M. Y.

Publications and source records attributed to Tan, G. M. Y..

3 recordsLinked to original sources

bioRxiv2026

Dual-antigen Doggybone DNA vaccine induces potent anti-tumor immunity against immunosuppressive oral cancer

Anti-PD1 blockade benefits only a subset of patients with head and neck squamous cell carcinoma (HNSCC), highlighting the need for approaches that overcome tumor immune resistance. Here, using the doggybone DNA (dbDNATM) platform, we developed CaVac OPT, an optimized dual-antigen DNA vaccine targeting MAGED4B and FJX1, which are overexpressed in most HPV-negative HNSCC and multiple solid tumors. In the MOC-2 oral cancer model, CaVac OPT significantly reduced tumor growth and when combined with anti-PD1 therapy, further delayed progression and improved survival. Immune profiling showed increased infiltration of CD4+ and CD8+ T cells, expansion of stem-like Tcf1+ populations, without increase in regulatory T cells, a reduced M2/M1 macrophage ratio and activation of interferon gamma associated pathways with suppression of tumor-promoting signals. These findings demonstrate that CaVac OPT reprograms the tumor microenvironment, converting cold HNSCC into T cell-inflamed responsive tumors. CaVac OPT represents a promising strategy for achieving durable control of aggressive, immunotherapy-resistant head and neck cancer.

cancer biology↗

bioRxiv2020

Functional analysis of promoters for driving long RNA transcripts in CAR T cells

Chimeric antigen receptor (CAR) T cell therapy is an effective treatment for B cell malignancies, with emerging potential for the treatment of other hematologic cancers and solid tumors. The strength of the promoter within the CAR cassette will alter CAR-polypeptide levels on the cell surface of the T cell - impacting on the kinetics of activation, survival and memory cell formation in T cells. In addition to the CAR, promoters can be used to drive other genes of interest to enhance CAR T cell function. Expressing multiple genes from a single RNA transcript can be effectively achieved by linking the genes via a ribosomal skip site. However, promoters may differ in their ability to transcribe longer RNAs, or could interfere with lentiviral production, or transduction frequencies. In this study we compared the ability of the strong well-characterized promoters CMV, EF-1, hPGK and RPBSA to drive functional expression of a single RNA encoding three products: GFP, CAR, plus an additional cell-survival gene, Mcl-1. Although the four promoters produced similarly high lentiviral titres, EF-1 gave the best transduction efficacy of primary T cells. Major differences were found in the ability of the promoters to drive expression of long RNA encoding GFP, CAR and Mcl-1, highlighting promoter choice as an important consideration for gene therapy applications requiring the expression of long and complex mRNA.

immunology↗

bioRxiv2018

Interleukin-17A Secreted from the Lung-infiltrating T Helper 17 Cells Renders Protective Immunity to Pulmonary Cryptococcus neoformans Infection

IL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate the activity of IL-17A in the protection against Cryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined if C. neoformans infection triggers IL-17A secretion in the in vitro setting using RAW264.7 murine macrophage cells, and in vivo using wildtype C57BL/6 mice. In addition, an enhanced green fluorescence protein (eGFP) reporter and a knockout (KO) mouse models were used to track the source of IL-17A secretion and explore the protective function of IL-17A, respectively. Our findings showed that both in vivo and in vitro models of C. neoformans infection demonstrated induction of abundant IL-17A secretion. By examining the lung bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A- EGFP reporter mice, we showed that intranasal inoculation with C. neoformans promoted leukocytes lung infiltration. A large proportion (~50%) of the infiltrated CD4+ helper T cell population secreted EGFP, indicating vigorous TH17 activity in the C. neoformans-infected lung. The infection study in IL-17A-KO mice, on the other hand, revealed that absence of IL-17A marginally boosted fungal burden in the lung and accelerated the mouse death. Therefore, our data suggest that IL-17A, released predominantly from TH17 cells in vivo, is essential in providing a protective immunity against C. neoformans infection.

immunology↗