Long-term follow up of patients treated with a DNA vaccine (pTVG-hp) for PSA-recurrent prostate cancer

Hum Vaccin Immunother. 2024 Dec 31;20(1):2395680. doi: 10.1080/21645515.2024.2395680. Epub 2024 Aug 29.

Abstract

We have previously reported two single-agent phase I trials, evaluating the dose or schedule, of a DNA vaccine (pTVG-HP) encoding prostatic acid phosphatase (PAP) administered with GM-CSF as the adjuvant. These were in patients with PSA-recurrent, radiographically non-metastatic, prostate cancer (PCa). We report here the long-term safety and overall survival of these patients. Specifically, 22 patients with non-metastatic, castration-sensitive PCa (nmCSPC) were treated with pTVG-HP, 100-1500 µg, administered over 12 weeks and followed for 15 y. 17 patients with non-metastatic castration-resistant PCa (nmCRPC) were treated with 100 µg pTVG-HP with different schedules of administration over 1 y and followed for 5 y. No adverse events were detected in long-term follow-up from either trial that were deemed possibly related to vaccination. Patients with nmCSPC had a median overall survival of 12.3 y, with 5/22 (23%) alive at 15 y. 8/22 (36%) died due to prostate cancer with a median survival of 11.0 y, and 9/22 (41%) died of other causes. Patients with nmCRPC had a median overall survival of 4.5 y, with 8/17 (47%) alive at 5 y. The presence of T-cells specific for the PAP target antigen was detectable in 6/10 (60%) individuals with nmCSPC, and 3/5 (60%) individuals with nmCRPC, many years after immunization. The detection of immune responses to the vaccine target years after immunization suggests durable immunity can be elicited in patients using a DNA vaccine encoding a tumor-associated antigen.Trial Registration: NCT00582140 and NCT00849121.

Keywords: DNA vaccine; long-term follow up; prostate cancer; prostatic acid phosphatase; survival.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Acid Phosphatase
  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Aged
  • Aged, 80 and over
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / adverse effects
  • Cancer Vaccines* / immunology
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prostate-Specific Antigen* / immunology
  • Prostatic Neoplasms* / immunology
  • Protein Tyrosine Phosphatases / immunology
  • Survival Analysis
  • Treatment Outcome
  • Vaccines, DNA* / administration & dosage
  • Vaccines, DNA* / adverse effects
  • Vaccines, DNA* / immunology

Substances

  • Vaccines, DNA
  • Prostate-Specific Antigen
  • Cancer Vaccines
  • Adjuvants, Immunologic
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • prostatic acid phosphatase
  • Acid Phosphatase
  • Protein Tyrosine Phosphatases

Associated data

  • ClinicalTrials.gov/NCT00582140
  • ClinicalTrials.gov/NCT00849121

Grants and funding

Grant support was provided by NIH [P50 CA269011, P30 CA014520, and R21 CA132267] and by the US Army Medical Research and Materiel Command Prostate Cancer Research Program [W81XWH-05-1-0404].