inducTION of mage‐A3 and HPV‐16 immunity by Trojan vaccines in patients with head and neck carcinoma

Voskens, Caroline J.; Sewell, David L.; Hertzano, Ronna; DeSanto, Jennifer; Rollins, Sandra; Lee, Myoung-Hee; Taylor, Rodney J.; Wolf, Jeffrey S.; Suntharalingam, Mohan; Gastman, Brian; Papadimitriou, John C.; Lu, Chi-Wei; Tan, Ming; Morales, Robert E.; Cullen, Kevin J.; Celis, Esteban; Mann, Dean L.; Strome, Scott E.

doi:10.1002/hed.22004

Cited by 63 publications

(56 citation statements)

References 32 publications

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“…Several peptide vaccines are under evaluation in HPV+ HNSCC. In a phase I trial, five patients with advanced HNSCC were treated with peptide vaccines composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or HPV-16 derived peptides, provoking a measurable immune response and acceptable toxicity (64). Furthermore, a phase II trial evaluating the efficacy of HPV16 E6 and E7 peptide vaccines in patients with HPV-related tumors including HNSCC has been completed and results are expected shortly (NCT00019110).…”

Section: Immunotherapeutic Strategies For Hpv-induced Hnsccmentioning

confidence: 99%

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Economopoulou¹,

Perisanidis²,

Giotakis³

et al. 2016

Ann. Transl. Med.

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Head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, with low survival rates for advanced stage tumors and minimal improvement in survival trends through the past decades. It is becoming increasingly clear that HNSCC oncogenesis and evolution is characterized by profound immune defects, as cancer cells evade immunosurveillance due to accumulation of genetic mutations and tumor heterogeneity. Improved understanding of the role of the immune system in cancer has led to the identification of novel therapeutic targets, which are being investigated for their potential to provide durable responses. In this review, we will summarize the role of the immune system in HNSCC, the rationale behind immunotherapy strategies and their clinical applications.

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Section: Immunotherapeutic Strategies For Hpv-induced Hnsccmentioning

confidence: 99%

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Economopoulou¹,

Perisanidis²,

Giotakis³

et al. 2016

Ann. Transl. Med.

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“…A phase I study attempted to combine HPV-16-derived peptides with the melanoma differentiation antigen MAGE-A3 into a therapeutic vaccine (33). Although there were no clinical responses in this small study, immune responses directed against the HPV epitopes targeted by the vaccine were detected, including T-cell responses in 4 of 5 treated patients.…”

Section: Immunotherapy As Treatment For Head and Neck Cancersmentioning

confidence: 88%

Immunity in Head and Neck Cancer

Schoenfeld

2015

Cancer Immunology Research

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Head and neck cancers are a diverse group of malignancies that includes an increasing number of virally mediated cancers in addition to tumors caused by tobacco and alcohol use. In both cases, tumor development is intimately related to the host immune system, and the status of an endogenous antitumor response is likely prognostic. Virally mediated cancers provide unique targets for preventive vaccines that generate immune responses directed against virus-associated antigens. Once head and neck tumors develop, they are commonly treated with surgery, radiotherapy, and/or chemotherapy. These treatments are associated with significant toxicities, and despite this, subgroups of patients respond poorly and are likely to relapse and die of their disease. Tumor immunotherapy may allow for improvements in both treatment-associated toxicity and outcome. In addition to providing specific targets for therapeutic vaccines and adoptive therapy, virally associated cancers may also be particularly dependent on immune checkpoints; therefore, immune checkpoint inhibitors are being actively tested for these diseases. Cancers that are not virally mediated may also respond to immunotherapies, and biomarkers that could predict response to immunotherapy irrespective of viral status are being evaluated. Multiple ongoing studies are testing benefits of immunotherapy in the management of metastatic squamous cell carcinoma of the head and neck. Early promising results pave the way for future studies that will expand testing to nonmetastatic diseases and other types of head and neck cancers. Prospects of combining various immunotherapies and more established treatments such as chemotherapy and radiotherapy are very intriguing and may provide synergistic benefits.

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“…As a result, E6/7 are fitting target TAAs for evoking HPV-specific cellular immune responses, particularly CD8 + cytotoxic T lymphocytes (CTLs), which are one of the major tumoricidal effector cell types. Multiple candidate vaccines targeting E6/7 are currently under development, including E6-and/or E7-derived peptide [42][43][44][45] , protein [46,47] , plasmid [48,49] and live-vectored vaccines [50][51][52][53] . Nevertheless, potential safety concerns for some of these vaccine models, especially for immunocompromised individuals, and the overall weak CD8 + CTL-mediated immunity -remain major challenges in developing a safe and effective vaccine against HPV-associated malignancies [54][55][56] .…”

Section: Malignant Transformation Of Hpv-infected Cells Is Drivenmentioning

confidence: 99%

Dendritic Cell Targeting Vaccine for HPV-Associated Cancer

Yin

Duluc

Joo

et al. 2017

Can Cell Microenviron

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Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients.Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8 + T cells, from the blood of HPV16 + head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16-associated malignancies. Dendritic cells (DCs) are the major antigen presenting cells (APCs) that can efficiently cross-prime antigen-specific CD8 + T cells [1,2] . Such functional specialty in turn makes DCs the ideal cellular targets for the rational design of vaccine against cancers. In line with these notions, Bonifaz et al. demonstrated that antigen targeting to in vivo DCs via DEC-205 using conjugates of anti-DEC-205 and antigen is far more efficient than antigen alone at eliciting antigen-specific cellular immunity [3] .For more than a decade after the initial report on DC targeting vaccines [3] , groups of scientists have been trying to RESEARCH HIGHLIGHTCancer Cell & Microenvironment 2016; 3: e1482. doi: 10.14800/ccm.1482; © 2016 by Wenjie Yin, et al.Page 2 of 6 optimize DC-targeting vaccines by delivering antigens to different DC surface receptors. These receptors include c-type lectins (e.g., DEC205, DC-SIGN, CD207, LOX-1, DC-ASGPR, Dectin-1, DCIR, DCIR2, CLEC6, CLEC9A, and CLEC12A) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][...

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inducTION of mage‐A3 and HPV‐16 immunity by Trojan vaccines in patients with head and neck carcinoma

Cited by 63 publications

References 32 publications

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

Immunity in Head and Neck Cancer

Dendritic Cell Targeting Vaccine for HPV-Associated Cancer

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