Neoantigens in immunotherapy and personalized vaccines: Implications for head and neck squamous cell carcinoma

Zolkind, Paul; Dunn, Gavin P.; Lin, Tianxiang; Griffith, Malachi; Griffith, Obi L.; Uppaluri, Ravindra

doi:10.1016/j.oraloncology.2016.09.010

Cited by 19 publications

(15 citation statements)

References 76 publications

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“…Not only have conventional shared cancer mutations been targeted by immunotherapy in HNSCCs, but also unique patient-specific mutations have generated increasing interest [ 110 ]. Advances in bioinformatics, in the prediction of what features define a ‘good’ MHC I or II binding epitope and better vaccine production technologies have all improved the practicality of targeting neoantigens.…”

Section: Non-viral Antigensmentioning

confidence: 99%

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Witzleben

Wang

Laban

et al. 2020

Cells

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Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignant tumours typically caused by alcohol and tobacco consumption, although an increasing number of HNSCC arise due to persistent infection with high-risk human papilloma virus (HPV). The treatment of HNSCC remains challenging, and the first-line setting is focused on surgery and chemoradiotherapy. A substantial proportion of HNSCC patients die from their disease, especially those with recurrent and metastatic disease. Among factors linked with good outcome, immune cell infiltration appears to have a major role. HPV-driven HNSCC are often T-cell rich, reflecting the presence of HPV antigens that are immunogenic. Tumour-associated antigens that are shared between patients or that are unique to an individual person may also induce varying degrees of immune response; studying these is important for the understanding of the interaction between the host immune system and the cancer. The resulting knowledge is critical for the design of better immunotherapies. Key questions are: Which antigens lead to an adaptive immune response in the tumour? Which of these are exploitable for immunotherapy? Here, we review the current thinking regarding tumour antigens in HNSCC and what has been learned from early phase clinical trials.

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Section: Non-viral Antigensmentioning

confidence: 99%

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Witzleben

Wang

Laban

et al. 2020

Cells

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“…Non-viral cancer antigens are largely divided into TSAs and TAAs [ 16 , 92 , 93 ]. TSA is a self-mutated protein (neoepitode) that is expressed only in cancer cells.…”

Section: Tumor Antigens Released By Ov Therapy Into the Tmementioning

confidence: 99%

“…P53 and RAS are frequently mutated in HPV-negative tumors [ 17 ]. Zolkind et al [ 16 ] proposed tumor-specific mutant antigen (TSMA). CASP8 is one example of a TSMA identified in human tumors whose mutation may be a driver mutation in HNSCC [ 94 , 95 ].…”

Section: Tumor Antigens Released By Ov Therapy Into the Tmementioning

confidence: 99%

“…However, in the KEYNOTE 012 trial for advanced cancer using an ICI, the overall response rate of the patients treated with the anti-PD-1 antibody was 18%, demonstrating that there are cases in which treatment alone is not curative [ 15 ]. New immunological therapies, such as antibodies that inhibit other immunosuppressive ligands, vaccine therapy and chimeric antigen receptor (CAR)-T cells, are also being investigated [ 4 , 8 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Efficient Delivery and Replication of Oncolytic Virus for Successful Treatment of Head and Neck Cancer

Hamada

Yura

2020

IJMS

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Head and neck cancer has been treated by a combination of surgery, radiation, and chemotherapy. In recent years, the development of immune checkpoint inhibitors (ICIs) has made immunotherapy a new treatment method. Oncolytic virus (OV) therapy selectively infects tumor cells with a low-pathogenic virus, lyses tumor cells by the cytopathic effects of the virus, and induces anti-tumor immunity to destroy tumors by the action of immune cells. In OV therapy for head and neck squamous cell carcinoma (HNSCC), viruses, such as herpes simplex virus type 1 (HSV-1), vaccinia virus, adenovirus, reovirus, measles virus, and vesicular stomatitis virus (VSV), are mainly used. As the combined use of mutant HSV-1 and ICI was successful for the treatment of melanoma, studies are underway to combine OV therapy with radiation, chemotherapy, and other types of immunotherapy. In such therapy, it is important for the virus to selectively replicate in tumor cells, and to express the viral gene and the introduced foreign gene in the tumor cells. In OV therapy for HNSCC, it may be useful to combine systemic and local treatments that improve the delivery and replication of the inoculated oncolytic virus in the tumor cells.

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“…Although therapeutic cancer vaccines showed promising results in animal models, they have conferred only modest anti-tumor activity in several human clinical trials for many cancers, including HNSCC [8][9][10]. Many of the previous approaches employed genetically modified allogeneic tumor cell lines or cell lines developed from patients or single tumor antigens or tumor antigen-specific peptides as vaccine sources [11].…”

Section: Introductionmentioning

confidence: 99%

Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer

et al. 2020

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Immune checkpoint inhibitor (ICI) immunotherapy improved the survival of head and neck squamous cell carcinoma (HNSCC) patients. However, more than 80% of the patients are still resistant to this therapy. To test whether the efficacy of ICI therapy can be improved by vaccine-induced immunity, we investigated the efficacy of a tumor membrane-based vaccine immunotherapy in murine models of HNSCC. The tumors, grown subcutaneously, are used to prepare tumor membrane vesicles (TMVs). TMVs are then incorporated with glycolipid-anchored immunostimulatory molecules GPI-B7-1 and GPI-IL-12 by protein transfer to generate the TMV vaccine. This TMV vaccine inhibited tumor growth and improved the survival of mice challenged with SCCVII tumor cells. The tumor-free mice survived for several months, remained tumor-free, and were protected following a secondary tumor cell challenge, suggesting that the TMV vaccine induced an anti-tumor immune memory response. However, no synergy with anti-PD1 mAb was observed in this model. In contrast, the TMV vaccine was effective in inhibiting MOC1 and MOC2 murine oral cancer models and synergized with anti-PD1 mAb in extending the survival of tumor-bearing mice. These observations suggest that tumor tissue based TMV vaccines can be harnessed to develop an effective personalized immunotherapy for HNSCC that can enhance the efficacy of immune checkpoint inhibitors.

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Neoantigens in immunotherapy and personalized vaccines: Implications for head and neck squamous cell carcinoma

Cited by 19 publications

References 76 publications

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Efficient Delivery and Replication of Oncolytic Virus for Successful Treatment of Head and Neck Cancer

Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer

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