scholarly journals Phase II Trial of a DNA Vaccine Encoding Prostatic Acid Phosphatase (pTVG-HP [MVI-816]) in Patients With Progressive, Nonmetastatic, Castration-Sensitive Prostate Cancer

2019 ◽  
Vol 37 (36) ◽  
pp. 3507-3517 ◽  
Author(s):  
Douglas G. McNeel ◽  
Jens C. Eickhoff ◽  
Laura E. Johnson ◽  
Alison R. Roth ◽  
Timothy G. Perk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Acid Phosphatase ◽  
Dna Vaccine ◽  
Specific Antigen ◽  
Standardized Uptake Value ◽  
Prostatic Acid Phosphatase ◽  
Ct Imaging ◽  
Gm Csf ◽  
Pet Ct

PURPOSE We previously reported the safety and immunologic effects of a DNA vaccine (pTVG-HP [MVI-816]) encoding prostatic acid phosphatase (PAP) in patients with recurrent, nonmetastatic prostate cancer. The current trial evaluated the effects of this vaccine on metastatic progression. PATIENTS AND METHODS Ninety-nine patients with castration-sensitive prostate cancer and prostate-specific antigen (PSA) doubling time (DT) of less than 12 months were randomly assigned to treatment with either pTVG-HP co-administered intradermally with 200 μg granulocyte-macrophage colony-stimulating factor (GM-CSF) adjuvant or 200 μg GM-CSF alone six times at 14-day intervals and then quarterly for 2 years. The primary end point was 2-year metastasis-free survival (MFS). Secondary and exploratory end points were median MFS, changes in PSA DT, immunologic effects, and changes in quantitative 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) imaging. RESULTS Two-year MFS was not different between study arms (41.8% vaccine v 42.3%; P = .97). Changes in PSA DT and median MFS were not different between study arms (18.9 v 18.3 months; hazard ratio [HR], 1.6; P = .13). Preplanned subset analysis identified longer MFS in vaccine-treated patients with rapid (< 3 months) pretreatment PSA DT (12.0 v 6.1 months; n = 21; HR, 4.4; P = .03). PAP-specific T cells were detected in both cohorts, including multifunctional PAP-specific T-helper 1–biased T cells. Changes in total activity (total standardized uptake value) on 18F-NaF PET/CT from months 3 to 6 increased 50% in patients treated with GM-CSF alone and decreased 23% in patients treated with pTVG-HP (n = 31; P = .07). CONCLUSION pTVG-HP treatment did not demonstrate an overall increase in 2-year MFS in patients with castration-sensitive prostate cancer, with the possible exception of a subgroup with rapidly progressive disease. Prespecified 18F-NaF PET/CT imaging conducted in a subset of patients suggests that vaccination had detectable effects on micrometastatic bone disease. Additional trials using pTVG-HP in combination with PD-1 blockade are under way.

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.

Randomized phase II trial of a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) versus GM-CSF adjuvant in patients with PSA-recurrent prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5037-5037 ◽  
Author(s):  
Glenn Liu ◽  
Lawrence Fong ◽  
Emmanuel S. Antonarakis ◽  
Jens C. Eickhoff ◽  
Ellen G. Wargowski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acid Phosphatase ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Bone Lesion ◽  
Prostatic Acid Phosphatase ◽  
Detectable Effect ◽  
Gm Csf ◽  
Randomized Phase Ii ◽  
Pet Ct

5037 Background: Phase I/II studies of pTVG-HP showed safety and increases in prostatic acid phosphatase (PAP)-specific T cells. Based on these, we conducted a multi-center, randomized phase II trial using pTVG-HP with GM-CSF adjuvant vs GM-CSF alone in patients with PSA-recurrent, non-metastatic, non-castrate, prostate cancer (stage M0). Methods: 99 patients with M0 prostate cancer (negative CT and bone scan) with PSA doubling time (DT) of < 12m were randomly assigned to pTVG-HP + GM-CSF vs GM-CSF. Treatments were every 2 wk x 6, and then quarterly for up to 24m. Primary endpoint was 2-year MFS. Secondary endpoints included median MFS, changes in PSA DT, and immune response to PAP antigen. Additional analysis included quantitative changes in bone lesion activity by NaF PET/CT. Results: Few grade 3/4 events were observed and were not statistically different between arms. 2-year MFS between control and pTVG-HP was 42.3% and 41.8% (p = 0.97). Median MFS was not different (18.3m control versus 18.9m pTVG-HP, HR = 1.6, p = 0.13). Changes in PSA DT, and immunity to the PAP target, were not different between study arms. A pre-planned subset analysis showed median MFS was significantly longer in patients with rapid PSA DT ( < 3m) treated with pTVG-HP (6.1m versus 12.0m, n = 21, HR = 4.4, p = 0.03). In patients with baseline metastases detected on NaF PET/CT, total activity (SUVtotal) increased 17% with GM-CSF alone, but decreased 29% with pTVG-HP from baseline to month 6 (n = 27, p = 0.07). Conclusions: This trial did not demonstrate an overall increase in 2-year MFS following treatment with pTVG-HP, but suggested a modest effect in patients with rapidly progressive disease. NaF PET/CT imaging suggests that pTVG-HP has a detectable effect on decreasing metastatic activity in bone. A separate trial suggests that pTVG-HP is an immune activating agent that improves activity of PD-1 blockade. A trial using pTVG-HP in combination with nivolumab in patients with M0 prostate cancer is currently underway. Clinical trial information: NCT01341652.

Plasmid DNA vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen-specific CD8+ T cells

2006 ◽  
Vol 56 (6) ◽  
pp. 885-895 ◽  
Author(s):  
Laura E. Johnson ◽  
Thomas P. Frye ◽  
Nachimuthu Chinnasamy ◽  
Dhanalakshmi Chinnasamy ◽  
Douglas G. McNeel
Keyword(s):  
T Cells ◽  
Acid Phosphatase ◽  
Dna Vaccine ◽  
Cd8 T Cells ◽  
Plasmid Dna ◽  
Prostatic Acid Phosphatase ◽  
Plasmid Dna Vaccine

DNA vaccine with pembrolizumab to elicit antitumor responses in patients with metastatic, castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 168-168 ◽  
Author(s):  
Douglas G. McNeel ◽  
Jens C. Eickhoff ◽  
Robert Jeraj ◽  
Mary Jane Staab ◽  
Jane Straus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Dna Vaccine ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Flt Pet ◽  
Pet Ct

168 Background: We have previously investigated a DNA vaccine encoding prostatic acid phosphatase (PAP, pTVG-HP) in patients with PSA-recurrent prostate cancer, and have demonstrated that this can be safely administered over many months and can elicit PAP-specific T cells. A phase 2 trial is currently underway. In preclinical models, we have found that blockade of regulatory receptors, including PD-1, at the time of T cell activation with vaccination produced anti-tumor responses in vivo. Similarly, we have recently found that patients with prostate cancer previously immunized with a DNA vaccine develop PD-1-regulated T cells. These findings suggested that combined PD-1 blockade with vaccination should elicit superior anti-tumor responses in patients with prostate cancer. Methods: A clinical trial was designed to evaluate the immunological and clinical efficacy of pTVG-HP when delivered in combination or in sequence with pembrolizumab, in patients with mCRPC. Serial biopsies, blood draws, and exploratory FLT PET/CT imaging are being conducted for correlative analyses. Results: While trial accrual continues, 1 of 14 subjects has experienced a grade 3 adverse event. There have been no grade 4 events. Several patients treated with the combination have experienced serum PSA declines, and several have experienced decreases in tumor volume by radiographic imaging at 12 weeks, including one partial response. Expansion of PAP-specific Th1-biased T cells has been detected in peripheral blood samples. Exploratory FLT PET/CT imaging has demonstrated proliferative responses in metastatic lesions and in vaccine-draining lymph nodes. Evaluation of biopsy specimens for recruitment of antigen-specific T cells is currently underway. Conclusions: PD-1 pathway inhibitors have demonstrated little clinical activity to date when used as single agents for treating prostate cancer. Our findings suggest that combining this blockade with tumor-targeted T-cell activation by a DNA vaccine is safe and can augment tumor-specific T cells, detectable within the peripheral blood and by imaging, and result in objective anti-tumor changes. Clinical trial information: NCT02499835.

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