scholarly journals P53-Synthetic Long Peptides Vaccine

2020 ◽  
Author(s):  
Keyword(s):  
Synthetic Long Peptides

Efficiency and Mechanism of Antigen-specific CD8+ T-cell Activation Using Synthetic Long Peptides

2012 ◽  
Vol 35 (2) ◽  
pp. 142-153 ◽  
Author(s):  
Maarten L. Zandvliet ◽  
Michel G. D. Kester ◽  
Ellis van Liempt ◽  
Arnoud H. de Ru ◽  
Peter A. van Veelen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Synthetic Long Peptides

scholarly journals Cancer vaccines: designing artificial synthetic long peptides to improve presentation of class I and class II T cell epitopes by dendritic cells

2019 ◽  
Vol 8 (4) ◽  
pp. e1560919 ◽  
Author(s):  
Catherine Rabu ◽  
Laurie Rangan ◽  
Laetitia Florenceau ◽  
Agnès Fortun ◽  
Maud Charpentier ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cancer Vaccines ◽  
Class Ii ◽  
Class I ◽  
T Cell Epitopes ◽  
Synthetic Long Peptides

scholarly journals Combination of Synthetic Long Peptides and XCL1 Fusion Proteins Results in Superior Tumor Control

2019 ◽  
Vol 10 ◽  
Author(s):  
Natalia K. Botelho ◽  
Benjamin O. Tschumi ◽  
Jeffrey A. Hubbell ◽  
Melody A. Swartz ◽  
Alena Donda ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Tumor Control ◽  
Synthetic Long Peptides

scholarly journals Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation

2013 ◽  
Vol 43 (10) ◽  
pp. 2554-2565 ◽  
Author(s):  
Rodney A. Rosalia ◽  
Esther D. Quakkelaar ◽  
Anke Redeker ◽  
Selina Khan ◽  
Marcel Camps ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Synthetic Long Peptides ◽  
Better Than

scholarly journals Self-Adjuvanting Cancer Vaccines from Conjugation-Ready Lipid A Analogues and Synthetic Long Peptides

2020 ◽  
Vol 63 (20) ◽  
pp. 11691-11706
Author(s):  
Niels R. M. Reintjens ◽  
Elena Tondini ◽  
Ana R. de Jong ◽  
Nico J. Meeuwenoord ◽  
Fabrizio Chiodo ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
Lipid A ◽  
Synthetic Long Peptides

Correlation between strength of T-cell response against HPV16 and survival after vaccination with HPV16 long peptides in combination with chemotherapy for late-stage cervical cancer.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Cornelis Joseph Melief ◽  
Winald R. Gerritsen ◽  
Marij Welters ◽  
Ignace Vergote ◽  
Judith R. Kroep ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cell ◽  
Late Stage ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Premalignant Lesions ◽  
Cell Responses ◽  
Number Of Patients ◽  
Synthetic Long Peptides

140 Background: Therapeutic vaccination with HPV type 16 synthetic long peptides (HPV16-SLP) results in T cell–mediated regression of HPV16-induced premalignant lesions but fails to install effective immunity in patients with advanced HPV16-positive cervical cancer. We showed that HPV16-SLP vaccination in mice and in patients with advanced cervical cancer patients fosters robust HPV16-specific T cell responses, when combined with chemotherapy. In this study we noted that a single dose of vaccine 2 weeks into the 2nd cycle of chemotherapy was optimal, because at this time the immunosuppressive myeloid cells were down. Methods: We now completed a chemo-immunotherapy study in a larger number of patients with late stage HPV16+ cervical cancer. Three HPV16-SLP vaccine doses were given 2 weeks after the second, third, and fourth cycles of standard chemotherapy. Cohorts of 12 patients each were vaccinated with each of 4 dose levels (20, 40, 100, and 300 µg/ per peptide) of 13 overlapping HPV16 synthetic long peptides (HPV16-SLP) together covering the length of the 2 E6 and E7 proteins. Results: Robust vaccine-induced HPV16-specific T cell responses as assessed by interferon-g Elispot were observed and were sustained throughout the cycles of chemotherapy. These T cell responses were substantially increased in all patients who received HPV16-SLP . In addition, the chemotherapy augmented recall responses to microbial antigens. Such robust T cell responses were not noted in previous trials when similar patients were vaccinated without timing of vaccination during chemotherapy. A marked correlation was observed between the strength of the vaccine-induced immune response and longer-term clinical outcomes such as overall survival. No such correlation exists between the strength of the T cell response against common recall antigens and survival. In addition, a remarkably high proportion of patients survived beyond 20 months after the start of therapy. Conclusions: These results indicate that the survival advantage is specifically related to the strength of the vaccine-induced T cell response and is not due to generally better immuno-competence. Clinical trial information: NCT02128126.

Phase I trial to determine safety and immunogenicity of amplivant, a synthetic toll-like receptor 2 ligand, conjugated to two HPV16 E6 synthetic long peptides.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2614-2614
Author(s):  
Frank M. Speetjens ◽  
Marij JP Welters ◽  
Marije Slingerland ◽  
Peggy de Vos van Steenwijk ◽  
Inge C.F.M. Roozen ◽  
...  
Keyword(s):  
T Cell ◽  
Dose Group ◽  
Phase I Trial ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Toll Like Receptor ◽  
Hpv16 E6 ◽  
Cell Immunity ◽  
Toll Like Receptor 2 ◽  
Synthetic Long Peptides

2614 Background: Therapeutic vaccines based on synthetic long peptides (SLPs) have a great potential for immunotherapy of cancer patients as these SLPs include both human leukocyte antigen (HLA) class I and II epitopes and no patient selection for HLA types is required. The antigen-induced immune response can be strengthened with immune stimulating additives. Amplivant (AV) is a synthetic Toll-like receptor 2 ligand which can be directly conjugated to tumor peptide antigens. In preclinical studies, AV-conjugation to antigens led to both enhanced antigen presentation by dendritic cells and T-cell priming and caused superior induction of effective anti-tumor responses. Moreover, AV-conjugated SLPs showed a 100 times higher immune response compared to unconjugated SLP. The current study is a first-in-human trial to investigate safety and immunogenicity of AV-conjugated human papillomavirus (HPV)16-SLPs. Methods: A dose escalation phase I trial was performed in 24 patients with HPV16 positive (pre-) malignant lesions. AV was conjugated to two SLPs derived from the most immunodominant regions of the HPV16 E6 oncoprotein. Four dose groups (1, 5, 20 or 50 μg of each peptide) in 6 patients each were studied. The vaccine was injected three times intradermally in DMSO / water with a three-week interval. Adverse events (AE) were collected according to CTCAE v4.0 up to 26 weeks. Peptide-specific T-cell immune responses were determined in blood samples taken before and after vaccination using complementary immunological assays (proliferation assay, IFNγ-ELISPOT and cytokine bead array). Results: Toxicity after three AV-conjugated HPV16-SLP vaccinations was limited to CTCAE grade 1 or 2, with predominantly inflammation at the vaccination site and sometimes flu-like symptoms, which generally resolved within one day. Dose increase resulted from no AE in the lowest dose group to mild/moderate AE in all vaccinated persons in the highest dose group. In the lowest dose group, minor vaccine-induced T-cell responses were observed in three of six vaccinated persons. In the highest dose group, all patients displayed a strong HPV16-specific T-cell response after vaccination. The induced T-cell response against HPV16 lasted until the end of the trial. Conclusions: This first-in-human study showed that AV conjugated to SLPs can safely be used as an intradermal therapeutic vaccine. AV-conjugated HPV16-SLP was able to induce robust HPV16-specific T-cell immunity in patients treated for HPV16 positive (pre-) malignancies without any other vaccine adjuvant or formulation. Increase in dose resulted in both a higher number of mild adverse events as well as stronger T-cell immunity. Clinical trial information: NCT02821494.

scholarly journals pDCs efficiently process synthetic long peptides to induce functional virus- and tumour-specific T-cell responses

2014 ◽  
Vol 44 (10) ◽  
pp. 2880-2892 ◽  
Author(s):  
Caroline Aspord ◽  
Claire Leloup ◽  
Sabine Reche ◽  
Joel Plumas
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Synthetic Long Peptides

Association of T cell responses after vaccination with HPV16 long peptides for late stage cervical cancer with prolonged survival.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5525-5525 ◽  
Author(s):  
Winald R. Gerritsen ◽  
Cornelis Joseph Melief ◽  
Marij Welters ◽  
Ignace Vergote ◽  
Judith R. Kroep ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cell ◽  
Late Stage ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Premalignant Lesions ◽  
Survival Duration ◽  
Cell Responses ◽  
Synthetic Long Peptides

5525 Background: Therapeutic vaccination with HPV type 16 synthetic long peptides (HPV16-SLP) results in T cell–mediated regression of HPV16-induced premalignant lesions but fails to install effective immunity in patients with advanced HPV16-positive cervical cancer. We showed that HPV16-SLP vaccination in mice and in patients with advanced cervical cancer patients fosters robust HPV16-specific T cell responses, when combined with chemotherapy (Welters et al. Sci. Transl. Med., 2016). Methods: We have now completed a chemo-immunotherapy study in 70 patients with late stage HPV16+ cervical cancer (clinical trials.gov NCT02128126). Three HPV16-SLP vaccine doses were given 2 weeks after the second, third and fourth cycle of standard chemotherapy (carboplatin, AUC 6; paclitaxel 175 mg/ m2). Cohorts of 12 patients each were vaccinated with each of 4 dose levels (20, 40, 100 and 300 µg/ per peptide) of 13 overlapping HPV16 synthetic long peptides (HPV16-SLP) together covering the length of the 2 E6 and E7 proteins. Two additional cohorts of 6 patients each were vaccinated with the most promising doses of 40 and 100 µg/ peptide. Results: Robust vaccine-induced HPV16-specific T cell responses as assessed by interferon-γ Elispot were observed and were sustained until at least 30 days after the 6th cycle of chemotherapy. In addition the chemotherapy augmented recall responses to microbial antigens. Such robust T cell responses were not noted in previous trials when similar patients were vaccinated without timing of vaccination during chemotherapy. A marked and significant positive correlation was observed between the strength of the vaccine-induced immune response and overall survival. No such correlation was observed between the strength of the T cell response against common recall antigens and survival. In addition a remarkably high proportion of patients survived beyond 2 years after the start of therapy. Conclusions: The results suggest that survival duration is directly related to the strength of the vaccine-induced HPV16-specific T cell response and is not due to generally better immuno-competence. Clinical trial information: NCT 02128126.

Sign in / Sign up

Export Citation Format

Share Document