Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma

Schlapbach, Christoph; Yerly, Daniel; Daubner, Barbara; Yawalkar, Nikhil; Hunger, Robert E.

doi:10.1016/j.jdermsci.2011.02.001

Cited by 22 publications

(12 citation statements)

References 43 publications

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“…Clinical trials using GV1001 suggest an increased survival in patients with cancer when combined with cytotoxic agents (42,43). Nevertheless, GV1001 vaccine also failed to induce specific immune responses and clinical benefit in other cancers (44). The impact of GV1001-specific CD4 þ T-cell help on antitumor CTL responses remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…The 4 peptides derived from TERT called UCPs: UCP1 (TERT [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] : PAAFRALVAQCLVCV), UCP2 (TERT 578-592 : KSVWSKLQSIGIRQH), UCP3 (TERT 916-930 : GTAFVQM-PAHGLFPW), and UCP4 (TERT 1041-1055 : SLCYSILKA-KNAGMS) have been described recently (19). The modified (first amino acid substitution with a tyrosine) HLA-A2-restricted pY988 (YLQVNSLQTV) and pY572 (YLFFYRKSV) peptides derived from TERT have been described elsewhere as high-affinity forms of their cryptic counterparts (23,24).…”

Section: Synthetic Peptidesmentioning

confidence: 99%

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Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor

Dosset

Godet

Vauchy

et al. 2012

Clinical Cancer Research

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Purpose: To evaluate CD4 þ helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT). Experimental Design: To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1 Ã 0101/HLA-A Ã 0201 transgenic mice were used to study the CD4 þ helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A Ã 0201-positive B16 melanoma that express TERT. Results:The presence of a high number of UCP-specific CD4 þ T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-g and TNF-a. In HLA transgenic mice, UCP vaccinations induced high avidity CD4 þ T H 1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A Ã 0201 melanoma and promotes tumor infiltration by TERTspecific CD8 þ T cells. Conclusions:Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers. Clin Cancer Res; 18(22); 6284-95. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Synthetic Peptidesmentioning

confidence: 99%

Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor

Dosset

Godet

Vauchy

et al. 2012

Clinical Cancer Research

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“…In a trial involving six patients with advanced CTCL and a telomerase‐specific peptide GV1001, five patients demonstrated a Th1 cytokine response. This was, however, not associated with a clinical response 120 …”

Section: Future and Emerging Therapiesmentioning

confidence: 70%

Cutaneous T cell lymphoma: update on treatment

Wollina

2012

Int J Dermatology

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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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Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma

Cited by 22 publications

References 43 publications

Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor

Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor

Cutaneous T cell lymphoma: update on treatment

A second chance for telomerase reverse transcriptase in anticancer immunotherapy

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