The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up

Si, Yongfeng; Deng, Zhuoxia; Lan, Guiping; Du, Haijun; Wang, Yongli; Si, Jinyuan; Wei, Jiazhang; Weng, Jingjin; Qin, Yangda; Huang, Bo; Yong, Yang; Qin, Ying

doi:10.1248/cpb.c16-00114

Cited by 37 publications

(35 citation statements)

References 25 publications

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“…The completed Phase 1 (NCT01147991, Table 1 ) trial showed safety, with only grade I/II adverse events. An immune response with increased circulating CD4 + T cells and antigen-specific T cell responses was reported [ 82 , 83 ]. A separate MVA-based vaccine study targeting EBNA1 and LMP2 led to increased CD4 + and CD8 + T-cell responses to at least one vaccine antigen in 15 of 18 patients [ 97 ].…”

Section: Virus-derived Tumour Antigensmentioning

confidence: 99%

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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: Virus-derived Tumour Antigensmentioning

confidence: 99%

“…Similarly, a recombinant Ad5-EBV-LMP2 vaccine was tested in NPC patients in a Phase 1 clinical trial and was well tolerated (NCT00078494, Table 1 ). Higher proportions of CD4 + T cells were detected in the high dosage group; however, no other functional tests have been done [ 82 ].…”

Section: Virus-derived Tumour Antigensmentioning

confidence: 99%

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Witzleben

Wang

Laban

et al. 2020

Cells

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“…1). 185,[220][221][222] Finally, a few studies preferred to use "unpulsed" autologous (matured ex vivo) DCs, administered in combination with cytokineinduced killer cells (CIKs), chemotherapy and/or radiotherapy. [223][224][225][226] Other approaches included the use of autologous dendritomas, 227 allogeneic peripheral blood mononuclear cells matured ex vivo into DCs, 228,229 or autologous unpulsed DCs combined with ACT.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

Trial watch: Dendritic cell-based anticancer immunotherapy

et al. 2017

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Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings. There is considerable clinical interest in combining DC-based anticancer vaccines with T cell-targeting immunotherapies. This reflects the established capacity of DC-based vaccines to generate a pool of TAA-specific effector T cells and facilitate their infiltration into the tumor bed. In this Trial Watch, we survey the latest trends in the preclinical and clinical development of DC-based anticancer therapeutics. We also highlight how the emergence of immune checkpoint blockers and adoptive T-cell transfer-based approaches has modified the clinical niche for DC-based vaccines within the wide cancer immunotherapy landscape.

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“…5,6 In the last decade, cancer immunotherapy has emerged as a clinically effective tool in several solid tumors, particularly in combination with more conventional therapies. 7 There are a variety of approaches in tumor immunotherapy, including manipulation of the immune system through the use of immune agents, such as vaccines, 8 cytokines, 9 checkpoint inhibitors (including anti-programmed death 1 [PD-1]/PD-ligand 1 [PD-L1] antibodies and anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4 antibodies 10,11 ), kinase inhibitors (such as apatinib and gefitinib), 12,13 and immune cells. [14][15][16][17][18][19][20] Among all the possible strategies, cellular immunotherapy has flourished and is widely used in tumor treatment, especially in Asia.…”

Section: Introductionmentioning

confidence: 99%

Rapid expansion in the WAVE bioreactor of clinical scale cells for tumor immunotherapy

Meng

Sun

et al. 2018

Human Vaccines & Immunotherapeutics

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Cell-based immunotherapy using natural killer (NK) cells, cytokine-induced killer (CIK) cells and dendritic cells (DCs) is emerging as a potential novel approach in the auxiliary treatment of a tumor. However, non-standard operation procedure, small-scale cell number, or human error may limit the clinical development of cell-based immunotherapy. To simplify clinical scale NK cells, CIK cells and DCs expansions, we investigated the use of the WAVE bioreactor, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. We developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant number of cells for our adoptive cell transfer clinical protocols. The high proliferative rate, surface phenotypes, and cytotoxicity of these immune cells, as well as the safety of cultivation were analyzed to illuminate the effect of WAVE bioreactor. The results demonstrated that the benefit of utilizing modern WAVE bioreactors in cancer immunotherapy was simple, safe, and flexible production.

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The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up

Abstract: Epstein-Barr virus (EBV)-

Cited by 37 publications

References 25 publications

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Trial watch: Dendritic cell-based anticancer immunotherapy

Rapid expansion in the WAVE bioreactor of clinical scale cells for tumor immunotherapy

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