Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells
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Updated: Mar 9, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Jon Amund Kyte1, Steinar Aamdal2, Svein Dueland2
1Department for Cell Therapy, Radiumhospitalet, Oslo University Hospital, Oslo, Norway; The Clinical Trial Unit, Radiumhospitalet, Oslo University Hospital, Oslo, Norway; Department of Immunology, Radiumhospitalet, Oslo University Hospital, Oslo, Norway.
Abstract:
The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n = 22) received the vaccine without any adjuvant; the next cohort (n = 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines. Immune response was evaluated by delayed-type hypersensitivity (DTH), T cell proliferation and cytokine assays. Data were collected for 10 y after inclusion of the last patient. No serious adverse events were detected. In the intention-to-treat-cohort, we demonstrated significantly superior survival compared to matched controls from a benchmark meta-analysis (1 y survival 43% vs. 24%, 2 y 23% vs. 6.6%). A tumor-specific immune response was demonstrated in 16/31 patients. The response rate was higher after intradermal than intranodal vaccination (80% vs. 38%). Immune responders had improved survival compared to non-responders (median 14 mo vs. 6 mo; p = 0.030), and all eight patients surviving >20 mo were immune responders. In addition to the tumor-specific response, most patients developed a response against autologous DC antigens. The cytokine profile was polyfunctional and did not follow a Th1/Th2 dichotomy. We conclude that the favorable safety profile and evidence of a possible survival benefit warrant further studies of the RNA/DC vaccine. The vaccine appears insufficient as monotherapy, but there is a strong rationale for combination with checkpoint modulators.
Insights
This study developed an RNA/dendritic cell (DC) vaccine for melanoma targeting patient-specific neoantigens. The vaccine showed a favorable safety profile and suggested improved survival, warranting further investigation, potentially in combination therapies.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Effective anticancer immune responses target patient-specific neoantigens.
- Dendritic cells (DCs) loaded with autologous tumor messenger RNA (mRNA) represent a promising strategy for personalized cancer vaccines.
Purpose of the Study:
- To evaluate the safety, immunogenicity, and clinical outcomes of an autologous tumor-mRNA-loaded dendritic cell (DC) vaccine in metastatic melanoma patients.
- To compare the efficacy of intranodal versus intradermal vaccination routes.
- To assess the potential for survival benefit and identify correlates of response.
Main Methods:
- A phase I/II clinical trial involving 31 metastatic melanoma patients.
- Vaccination involved four weekly intranodal or intradermal injections of autologous tumor-mRNA-loaded DCs, with optional monthly boosters.
- Some patients received adjuvant interleukin-2 (IL2).
- Immune responses were assessed via delayed-type hypersensitivity (DTH), T cell proliferation, and cytokine assays.
- Survival data were collected for 10 years post-enrollment.
Main Results:
- The RNA/DC vaccine demonstrated a favorable safety profile with no serious adverse events.
- One-year and two-year survival rates in the intention-to-treat cohort were 43% and 23%, respectively, significantly outperforming matched controls (24% and 6.6%).
- Tumor-specific immune responses were observed in 16 out of 31 patients, with a higher response rate for intradermal delivery (80%) compared to intranodal (38%).
- Immune responders exhibited significantly improved survival (median 14 months vs. 6 months for non-responders; p = 0.030).
- All patients surviving longer than 20 months were immune responders.
- A polyfunctional cytokine profile was observed, not adhering to a Th1/Th2 dichotomy.
Conclusions:
- The autologous tumor-mRNA-loaded DC vaccine exhibits a favorable safety profile and suggests a potential survival benefit in metastatic melanoma.
- Intradermal vaccination appears more effective in eliciting tumor-specific immune responses.
- The vaccine may be insufficient as monotherapy, but combination with checkpoint modulators presents a strong rationale for future clinical development.
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