Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients.
Level 2 - randomized trial
Randomized phase 1/2 trial comparing two vaccine formulations
PubMed 19609242 · doi:10.1097/CJI.0b013e3181a00068
What was done
Twenty-one patients with metastatic melanoma received intradermal injections of protamine-stabilized mRNAs coding for six tumor antigens (Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin) with granulocyte macrophage colony-stimulating factor (GM-CSF) as an adjuvant. Ten patients received keyhole limpet hemocyanin (KLH) added to the vaccine formulation. Endpoints were toxicity and immune responses.
What was found
No adverse events greater than grade II were observed. Foxp3+/CD4+ regulatory T cells significantly decreased in the peripheral blood of patients in the KLH arm, while myeloid suppressor cells (CD11b+HLA-DR lo monocytes) were reduced in patients not receiving KLH (exact numbers and p-values not reported in abstract). A reproducible increase in vaccine-directed T cells was observed in 2 of 4 immunologically evaluable patients. One of 7 patients with measurable disease achieved a complete response.
Why it matters
This trial provides early proof-of-concept that direct intradermal injection of protamine-protected mRNA is safe and can modulate circulating immunosuppressive cells and induce tumor antigen-specific immune responses in patients with metastatic melanoma.
Limits
The study had a very small sample size (n = 21 overall; 4 evaluable for T-cell responses; 7 evaluable for measurable tumor response). The abstract does not provide exact numerical values, confidence intervals, or p-values for immunological changes.
Cited by
- contradicts In 2014, the first clinical trial using an mRNA vaccine as immunotherapy for cancer in humans was conducted.
- supports In 2009, a human clinical trial was conducted evaluating mRNA as a therapeutic.