# Novel strategy combined with targeted radiation therapy unleashes potent antitumor immunity in HPV + head and neck cancer > **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $229,659 ## Abstract Project Summary/Abstract The overwhelming public health burden of HPV-associated head and neck cancer (HNC) has created great demand for novel, broadly effective therapies with reduced treatment morbidity and improved long term survival. While targeting HPV antigens in HPV+ cancers may be intuitive, these strategies have not demonstrated clear treatment efficacy, potentially due to the importance of neoantigen-specific cytotoxic T cell immunity in the long- term control of all cancers, including viral-associated cancer (1). Devising an off-the-shelf, broadly effective therapeutic strategy that can easily be combined with standard-of-care chemoradiation and is capable of potentiating both HPV- and neoantigen-specific CD8+ T cell immunity in HPV-associated HNC could prove widely efficacious. The generation of tumor-specific CD8+ T cell immunity requires potent antigen presentation by dendritic cells (DCs) since tumor cells do not efficiently present relevant CD8+ T cell epitopes. Murine CD103+ and CD8a+ DCs (cDC1s) are known for their ability to process exogenous antigen and potently cross-present to CD8+ T cells. Because of this, innovative strategies to enhance cross-presenting DC subsets could robustly induce HPV- and neoantigen-specific immunity and have great therapeutic potential in the treatment of HPV- associated HNC. FMS-like tyrosine kinase 3 ligand (Flt3L) is a cytokine that expands and differentiates DC precursors to murine cDC1s, but therapeutic potential of Flt3L is limited because of its short half-life and global distribution in vivo. We have overcome the described issues of Flt3L by generating a genetic fusion of Albumin (Alb) to Flt3L, named Albumin-Flt3L (Alb-Flt3L). Alb has a long half-life due to neonatal Fc receptor (FcRn)- mediated transcytolic recycling, and exhibits trafficking to the LNs as a serum protein. The novel immunotherapeutic Alb-Flt3L fusion protein exhibits increased half-life and selective accumulation in LN and tumor compared to native Flt3L. Alb-Flt3L is able to expand cross-presenting DC populations in vivo following a single injection. Alb-Flt3L + targeted radiation therapy (RT) to release tumor antigens and enhance tumor immunogenicity is able to control tumor progression and extend survival of colon adenocarcinoma MC38 tumor bearing mice. Impressively, Alb-Flt3L + RT induced spontaneous tumor neoantigen-specific T cell responses, in addition to efficacy as a single agent in PANC02 model. In this proposal, the ability of Alb-Flt3L to promote HPV- and neoantigen-specific cytotoxic T cell antitumor immunity through the expansion of cross-presenting DCs and subsequent tumor control in multiple HPV-associated HNC models will be investigated. HPV- and neoantigen- specific CD8+ T cell responses will be evaluated using tetramer and TCR sequencing approaches. The mechanism by which Alb-Flt3L mediates its immunostimulatory function will also be interrogated using appropriate deficient mouse models. Successful compl... ## Key facts - **NIH application ID:** 10285000 - **Project number:** 1R21CA256020-01A1 - **Recipient organization:** JOHNS HOPKINS UNIVERSITY - **Principal Investigator:** Chien-Fu Hung - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $229,659 - **Award type:** 1 - **Project period:** 2021-07-01 → 2023-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10285000 ## Citation > US National Institutes of Health, RePORTER application 10285000, Novel strategy combined with targeted radiation therapy unleashes potent antitumor immunity in HPV + head and neck cancer (1R21CA256020-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10285000. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*