Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients

Staff, Caroline; Mozaffari, Fariba; Frödin, Jan‐Erik; Mellstedt, Håkan; Liljefors, Maria

doi:10.3892/ijo.2014.2496

Cited by 62 publications

(39 citation statements)

References 40 publications

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“…Several hTERT vaccines have incorporated helper peptides and have induced Th1 T CD4 responses [51–53], as well as epitope spreading to Ras peptides [51]. One hTERT vaccine enhanced DC activation in preclinical models, including IL-12 production [54].…”

Section: Clinical Experience With Helper Peptide Vaccinesmentioning

confidence: 99%

Vaccines targeting helper T cells for cancer immunotherapy

Melssen

Slingluff

2017

Current Opinion in Immunology

160

145

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There are compelling arguments for designing cancer vaccines specifically to induce CD4+ helper T cell responses. Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4+ T cells in effective antitumor immunity and reveal that CD4+ T cells induce more durable immune-mediated tumor control than CD8+ T cells. CD4+ T cells promote antitumor immunity by numerous mechanisms including enhancing antigen presentation, co- stimulation, T cell homing, T cell activation, and effector function. These effects are mediated at sites of T cell priming and at the tumor microenvironment. Several cancer vaccine approaches induce durable CD4+ T cell responses and have promising clinical activity. Future work should further optimize vaccine adjuvants and combination therapies incorporating helper peptide vaccines.

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Section: Clinical Experience With Helper Peptide Vaccinesmentioning

confidence: 99%

Vaccines targeting helper T cells for cancer immunotherapy

Melssen

Slingluff

2017

Current Opinion in Immunology

160

145

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“…Objective clinical responses were reported in four phase I/I-II studies with distinct designs, in a variable percentage (8-71%) of the evaluable vaccinees [59][60][61][62][63] . No objective responses were reported in the other phase I/I-II studies in which clinical outcomes were assessed (n = 6) [64][65][66][67][68][69] . Disease stabilization in >50% of the evaluable patients vaccinated was reported in two studies (rates of 67% and 83%) 59,69 , whereas lower rates of disease stabilization (16-48%) have been observed in seven studies (TABLE 1).…”

Section: Autoimmunity and Tert Vaccinesmentioning

confidence: 99%

A second chance for telomerase reverse transcriptase in anticancer immunotherapy

Zanetti¹

2016

Nat Rev Clin Oncol

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Telomerase reverse transcriptase (TERT) is a self-antigen that is expressed constitutively in many tumours, and is, therefore, an important target for anticancer immunotherapy. In the past 10 years, trials of immunotherapy with TERT-based vaccines have demonstrated only modest benefits. In this Perspectives, I discuss the possible immunological reasons for this limited antitumour efficacy, and propose that advances in our understanding of the genetics and biology of the involvement of TERT in cancer provides the basis for renewed interest in TERT- based immunotherapy. Telomerase and TERT are expressed in cancer cells at every stage of tumour evolution, from the cancer stem cell to circulating tumour cells and tumour metastases. Many cancer types also harbour cells with mutations in the TERT promoter region, which increase transcriptional activation of this gene. These new findings should spur new interest in the development of TERT-based immunotherapies that are redesigned in line with established immunological considerations and working principles, and are tailored to patients stratified on the basis of TERT-promoter mutations and other underlying tumour characteristics. Thus, despite the disappointment of previous clinical trials, TERT offers the potential for personalized immunotherapy, perhaps in combination with immune-checkpoint inhibition.

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“…Mild adverse events were observed, and a GV1001-specific immune response, albeit transient, was reported in 75% of patients who contextually received GV1001, GM-CSF, and gemcitabine. 88 The multicenter Phase III trial of the GV1001 vaccine in advanced and metastatic PDA recruited 1,062 patients in 52 centers throughout the UK. There was no significant difference in the overall survival between the groups that received the vaccine and the control group receiving chemotherapy, but two biomarkers that defined responders to the vaccine were identified.…”

Section: Peptide Vaccines and Adoptive Transfer Therapymentioning

confidence: 99%

Pancreatic cancer vaccine: a unique potential therapy

Cappello¹,

Principe²,

Novelli³

2015

GICTT

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Pancreatic ductal adenocarcinoma (PDA) is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological checkpoints. Keywords: pancreatic cancer, vaccines, T-cells, antibody, immunotherapy Pancreatic cancerAlthough lung, breast, prostate, and colorectal cancers are considered to be the "big four" cancer types in the USA, pancreas and liver cancers are expected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related deaths by 2030, respectively.1 Pancreatic ductal adenocarcinomas (PDAs) arise from the exocrine pancreas and account for 95% of pancreatic cancers. In the USA, there were an estimated 48,960 cases of new-onset pancreatic cancer in 2015, which led to 40,560 deaths, with a 5-year survival rate of ∼7%.3 PDA is nearly universally lethal; ,20% of patients are suitable candidates for surgery at the time of diagnosis, and the median survival rate is 3.5 months and 12.6 months for nonresected patients and resected patients, respectively.2,4 PDA evolves from noninvasive precursor lesions that do not invade the basement membrane. [5][6][7] Three precursors have been characterized, namely, pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms.

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Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients

Cited by 62 publications

References 40 publications

Vaccines targeting helper T cells for cancer immunotherapy

Vaccines targeting helper T cells for cancer immunotherapy

A second chance for telomerase reverse transcriptase in anticancer immunotherapy

Pancreatic cancer vaccine: a unique potential therapy

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