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Published on: March 6, 2018
Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients
1Section for Immunotherapy, The Norwegian Radium Hospital, University of Oslo, Montebello.
Abstract:
Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n = 19, P = 0.002, r = 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.
Insights
This study shows a new prostate cancer vaccine using mRNA-transfected dendritic cells (DCs) is safe and effective. It generated immune responses and lowered prostate-specific antigen (PSA) levels in patients, suggesting a potential new treatment.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Prostate cancer remains a significant health concern.
- Current treatments have limitations, necessitating novel therapeutic approaches.
- Dendritic cell (DC) based vaccines offer a promising avenue for cancer immunotherapy.
Purpose of the Study:
- To evaluate the safety and feasibility of a novel dendritic cell (DC) vaccination strategy for prostate cancer.
- To assess the immunogenicity of DCs transfected with mRNA from allogeneic prostate cancer cell lines.
- To explore the correlation between immune responses and clinical outcomes, including prostate-specific antigen (PSA) levels.
Main Methods:
- A clinical trial involving 20 prostate cancer patients.
- Vaccination with mRNA-transfected allogeneic prostate cancer cell line DCs (DU145, LNCaP, PC-3).
- Administration of at least four weekly injections (intranodal or intradermal) of 2 x 10(7) transfected DCs.
- Monitoring of safety, immune responses (delayed-type hypersensitivity, ELISPOT, T-cell proliferation), PSA levels, and bone scans.
Main Results:
- The vaccination was safe and feasible, with no observed toxicity or serious adverse events.
- 12 out of 19 patients developed specific immune responses to tumor mRNA-transfected DCs.
- 13 patients showed a decrease in log slope PSA, with booster vaccinations enhancing this effect.
- Clinical outcome was significantly correlated with immune responses (P = 0.002, r = 0.68).
Conclusions:
- Vaccination with mRNA-transfected DCs is safe and elicits cellular immune responses specific to prostate cancer antigens.
- The observed effect on PSA levels suggests potential as a therapeutic modality for prostate cancer.
- This approach warrants further investigation as a novel treatment strategy for prostate cancer patients.
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