scholarly journals DNA Vaccine Encoding Prostatic Acid Phosphatase (PAP) Elicits Long-term T-cell Responses in Patients With Recurrent Prostate Cancer

2010 ◽  
Vol 33 (6) ◽  
pp. 639-647 ◽  
Author(s):  
Jordan T. Becker ◽  
Brian M. Olson ◽  
Laura E. Johnson ◽  
James G. Davies ◽  
Edward J. Dunphy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acid Phosphatase ◽  
T Cell ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Prostatic Acid Phosphatase ◽  
Recurrent Prostate Cancer ◽  
Cell Responses

scholarly journals Safety and Immunological Efficacy of a DNA Vaccine Encoding Prostatic Acid Phosphatase in Patients With Stage D0 Prostate Cancer

2009 ◽  
Vol 27 (25) ◽  
pp. 4047-4054 ◽  
Author(s):  
Douglas G. McNeel ◽  
Edward J. Dunphy ◽  
James G. Davies ◽  
Thomas P. Frye ◽  
Laura E. Johnson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Acid Phosphatase ◽  
T Cell ◽  
Dna Vaccine ◽  
Cd8 T Cells ◽  
Doubling Time ◽  
Prostatic Acid Phosphatase ◽  
T Cell Response ◽  
Psa Doubling Time

Purpose Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer. Patients and Methods Twenty-two patients were treated in a dose-escalation trial with 100 μg, 500 μg, or 1,500 μg plasmid DNA, coadministered intradermally with 200 μg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment. Results No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFNγ-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054). Conclusion The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.

A plasmid DNA vaccine encoding prostatic acid phosphatase (PAP) elicits antigen-specific T cells in patients with stage D0 prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14570-14570
Author(s):  
D. G. McNeel ◽  
E. J. Dunphy ◽  
L. E. Johnson ◽  
T. P. Frye ◽  
M. J. Staab ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Prostatic Acid Phosphatase ◽  
T Cell Proliferation ◽  
Cell Responses ◽  
Plasmid Dna Vaccine ◽  
Specific Igg ◽  
Minimal Residual

14570 Background: Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer. Clinical trials conducted in patients with metastatic prostate cancer targeting PAP by means of antigen presenting-cell vaccines have suggested clinical benefit in terms of disease progression and overall survival. Ultimately, tumor vaccines may be most effective in the setting of minimal residual disease. We have been investigating plasmid DNA vaccines encoding PAP in rodent models. We found these to be safe and effective in eliciting PAP-specific CD8 T cells and saw evidence of anti-tumor efficacy. We report here the initial immunological results from a dose-escalation portion of a phase I trial testing a DNA vaccine encoding PAP in patients with minimal residual stage D0 prostate cancer. Methods: Patients with clinical stage D0 prostate cancer with rising PSA were vaccinated over a 12-week period, 6 times at 14-day intervals, with a plasmid DNA vaccine encoding PAP (pTVG-HP). Vaccinations were administered intradermally with 100 mcg, 500 mcg, or 1500 mcg doses, and with 200 mcg of GM-CSF co-administered as a vaccine adjuvant. Immunological responses were evaluated by antigen-specific T cell proliferation and IFNγ secretion, and by ELISA for PAP-specific IgG. Results: At present 9 patients have been enrolled in a dose-escalation portion of the trial, and 6 have completed all immunizations. No serious adverse events have been observed, and no patients have discontinued treatment. To date, immunological analysis has been performed for the first, lowest dose cohort. PAP-specific CD4 and CD8 T cell responses, measured by antigen-specific T cell proliferation, were elicited following immunization in 2 of 3 patients. PAP-specific IgG antibodies were not detectable in these patients following vaccination. Conclusions: Intradermal immunization of patients with stage D0 prostate cancer with pTVG-HP has been without evidence of adverse events in doses up to 500 mcg. CD4 and CD8 T cell responses have been observed, consistent with a predominantly cellular immune response, at even the lowest dose of vaccine. Immunological analysis will be performed for patients completing the other dose levels, and all patients will be followed for changes in serum PSA levels. No significant financial relationships to disclose.

scholarly journals Long-Term Central and Effector SHIV-Specific Memory T Cell Responses Elicited after a Single Immunization with a Novel Lentivector DNA Vaccine

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110883 ◽  
Author(s):  
Géraldine Arrode-Brusés ◽  
Maha Moussa ◽  
Monique Baccard-Longere ◽  
François Villinger ◽  
Yahia Chebloune
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Memory T Cell ◽  
Cell Responses ◽  
Specific Memory

Analysis of PSA-Specific T-Cell Responses of Prostate Cancer Patients Given a PSA-Based Vaccine on a Clinical Trial

2003 ◽  
Author(s):  
James Gulley ◽  
William Dahut ◽  
Philip M. Arlen ◽  
Kwong Tsang ◽  
Jeffrey Schlom
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cell ◽  
Cancer Patients ◽  
T Cell Responses ◽  
Cell Responses

scholarly journals Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 307
Author(s):  
Yong Bok Seo ◽  
You Suk Suh ◽  
Ji In Ryu ◽  
Hwanhee Jang ◽  
Hanseul Oh ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Viral Loads ◽  
Cell Responses ◽  
Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

scholarly journals Long-Term Immunity to Trypanosoma cruzi in the Absence of Immunodominanttrans-Sialidase-Specific CD8+T Cells

2016 ◽  
Vol 84 (9) ◽  
pp. 2627-2638 ◽  
Author(s):  
Charles S. Rosenberg ◽  
Weibo Zhang ◽  
Juan M. Bustamante ◽  
Rick L. Tarleton
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Trypanosoma Cruzi ◽  
T Cell Responses ◽  
Content Type ◽  
Cell Responses ◽  
Pathogen Control ◽  
Immunodominant Epitopes

Trypanosoma cruziinfection drives the expansion of remarkably focused CD8+T cell responses targeting epitopes encoded by varianttrans-sialidase (TS) genes. Infection of C57BL/6 mice withT. cruziresults in up to 40% of all CD8+T cells committed to recognition of the dominant TSKB20 and subdominant TSKB18 TS epitopes. However, despite this enormous response, these mice fail to clearT. cruziinfection and subsequently develop chronic disease. One possible reason for the failure to cureT. cruziinfection is that immunodomination by these TS-specific T cells may interfere with alternative CD8+T cell responses more capable of complete parasite elimination. To address this possibility, we created transgenic mice that are centrally tolerant to these immunodominant epitopes. Mice expressing TSKB20, TSKB18, or both epitopes controlledT. cruziinfection and developed effector CD8+T cells that maintained an activated phenotype. Memory CD8+T cells from drug-cured TSKB-transgenic mice rapidly responded to secondaryT. cruziinfection. In the absence of the response to TSKB20 and TSKB18, immunodominance did not shift to other known subdominant epitopes despite the capacity of these mice to expand epitope-specific T cells specific for the model antigen ovalbumin expressed by engineered parasites. Thus, CD8+T cell responses tightly and robustly focused on a few epitopes within variant TS antigens appear to neither contribute to, nor detract from, the ability to controlT. cruziinfection. These data also indicate that the relative position of an epitope within a CD8+immunodominance hierarchy does not predict its importance in pathogen control.

Sign in / Sign up

Export Citation Format

Share Document