A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma

Chia, Whay Kuang; Wang, W.-W.; Teo, Melissa Ching Ching; Tai, Wai Meng David; Lim, Darren Wan-Teck; Tan, Eng Huat; Leong, S. S.; Lee, Sun; Chen, J. J.; Gottschalk, Stephen; Toh, Han Chong

doi:10.1093/annonc/mdr341

Cited by 119 publications

(95 citation statements)

References 36 publications

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“…More recently, a phase II clinical trial in 16 patients with metastatic carcinoma has evaluated the efficacy of autologous dendritic cells transduced with an adenovirus expressing truncated LMP1 and full-length LMP2. Although this vaccine was safe and immunogenic, it showed limited efficacy, with only 3 subjects responding to the treatment [55]. …”

Section: Ebv Immunotherapy For Nasopharyngeal Carcinomamentioning

confidence: 99%

Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies

et al. 2015

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Tobacco use and alcohol consumption are the main risk factors associated with head and neck squamous cell carcinoma (SCC) development due to their cytotoxic and mutagenic effects on the exposed epithelia of the upper aerodigestive tract. Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs), both encoding viral oncoproteins able to interfere with cell cycle control, have been recognized as the etiological agents of nasopharynx carcinoma and a fraction of oropharyngeal carcinoma, respectively. Head and neck SCC is a deadly disease and despite innovative treatments represents a major challenge for patients. Recently, a number of genomic studies have highlighted the molecular heterogeneity of head and neck SCC based on methylation profiles, microRNA expression, mutated genes and new druggable pathways which may represent new targets for cancer-tailored therapies. To date, cetuximab is the only FDA-approved anti-epidermal growth factor receptor therapy for the treatment of head and neck SCC. In addition, a number of monoclonal antibodies targeting AKT, mTOR and PI3K pathways are under evaluation. Several therapeutic vaccines against HPV16 and EBV proteins are also under study. The purpose of this article is to review the epidemiology, pathogenesis and molecular features of head and neck SCC, with an emphasis on new therapies.

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Section: Ebv Immunotherapy For Nasopharyngeal Carcinomamentioning

confidence: 99%

Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies

et al. 2015

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“…These studies have provided evidence of potential improved efficacy in these cohorts of patients. A recent Phase II study by Chia et al used T-cell therapy as an adjunct to standard chemotherapy in first-line treatment [65]. Following four cycles of gemcitabine and carboplatin, patients received up to six doses of EBV-CTL.…”

Section: Review Smith and Khannamentioning

confidence: 99%

Adoptive Therapy for EBV-Induced Cancers: Driving Success with Post-Transplant Lymphoproliferative Disorder to Other EBV-Derived Tumors

Smith

Khanna

2015

Immunotherapy

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Epstein-Barr virus (EBV) infection is associated with a range of human malignancies of lymphocytic and epithelial cell origin. In addition to viral-mediated and genetic oncogenic events that lead to the establishment of EBV-associated malignancies, defects in the immune control of EBV likely play a significant role in promoting the survival of malignant cells. This breakdown in immune surveillance is most evident in immunocompromised transplant patients who are susceptible to the development of post-transplant lymphoproliferative disorders. Observations over the last two decades have shown that reconstitution of EBV-specific cellular immunity via adoptive cell therapy can have a dramatic effect on both preventing and treating post-transplant lymphoproliferative disorders, leading to hope that similar strategies could be effective in preventing more prevalent EBV-associated malignancies.

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“…A similar recent study using LMP2-pulsed DC also showed an increase in the LMP2 response, while this did not correlate with a reduction in the peripheral EBV load, there was evidence that the induction of a delayed-type hypersensitivity (DTH) response did correlate to a reduction in EBV load (Li et al 2013). Another approach using DC involved transduction with an adenoviral vector encoding a truncated LMP1 (ΔLMP1) and full-length LMP2 (Chia et al 2011). In this phase II study, 9 of 12 NPC patients generated a DTH response.…”

Section: Immunisation Of Npc Patients With Dendritic Cell-based Vaccinesmentioning

confidence: 92%

The Development of Prophylactic and Therapeutic EBV Vaccines

Smith

Khanna

2015

Epstein Barr Virus Volume 2

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Over the last century, the development of effective vaccine approaches to treat a number of viral infections has provided the impetus for the continual development of vaccine platforms for other viral infections, including Epstein-Barr virus (EBV). The clinical manifestations associated with EBV infection occur either following primary infection, such as infectious mononucleosis, or following an extended period of latency, primarily the EBV-associated malignancies and potentially including a number of autoimmune disorders, such as multiple sclerosis. As a consequence, two independent vaccine approaches are under development to prevent or control EBV-associated diseases. The first approach, which has been widely successful against other viral infections, is aimed at inducing a viral neutralisation antibody response to prevent primary infection. The second approach focuses upon the induction of cell-mediated immunity to control latent infected cells in persistently infected individuals. Early clinical studies have offered some insight into the potential efficacy of both of these approaches.

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A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma

Cited by 119 publications

References 36 publications

Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies

Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies

Adoptive Therapy for EBV-Induced Cancers: Driving Success with Post-Transplant Lymphoproliferative Disorder to Other EBV-Derived Tumors

The Development of Prophylactic and Therapeutic EBV Vaccines

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