Existing therapies targeting the mutated BRAF oncodriver (BRAF) successfully treat melanoma but are susceptible to resistance. This study assessed the potential of a dendritic cell-based BRAF vaccine for the treatment of BRAF-mutant melanoma. Type 1-polarized dendritic cells (DC1) pulsed with affinity-modified BRAF peptide were administered to C57Bl/6 mice both before (prevention) and twice weekly after (treatment) the development of established tumor with B16 melanoma transfected to express BRAF (B16). The efficacy of the BRAF-pulsed DC1 vaccine was corroborated in a novel transplantable BRAF-mutant murine melanoma model (BRAF; PTEN; CDK2NA). Three-dimensional tumor measurements and survival were determined. Induction of BRAF-specific CD8 T-cell responses after brief in-vitro sensitization was assessed by interferon-γ enzyme-linked immunosorbent assay and/or enzyme-linked immunospot. Mice receiving BRAF-pulsed DC1 vaccines before B16 tumor challenge demonstrated increased tumor-doubling times (P<0.001) and improved survival (P=0.0186) compared with those that received ovalbumin (control)-pulsed DC1 vaccines. In mice bearing established B16 tumors (mean 32 mm), BRAF-pulsed DC1 vaccines delayed tumor growth (P<0.001) and improved survival (P=0.0008), compared with untreated mice. Likewise, in mice bearing BRAF; PTEN; CDK2NA tumors, compared with controls, BRAF-DC1 vaccination recapitulated these effects by delaying tumor growth (P<0.001) and improving survival (P=0.002). Vaccination elicited specific CD8 T-cell recognition of BRAF-pulsed antigen-presenting cells (P<0.05), as well as BRAF-expressing cancer cells (P<0.001), measured by interferon-γ release in vitro. BRAF-pulsed DC1 vaccines induce oncogene-specific CD8 T-cell immune responses that impact tumor growth and survival in preclinical models of BRAF-mutant melanoma. Exploration of BRAF-targeted vaccines, in combination with BRAF-targeted therapies and checkpoint inhibitors, is warranted.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 January 2025.
All research outputs
#7,356,343
of 25,374,647 outputs
Outputs from Melanoma Research
#169
of 1,128 outputs
Outputs of similar age
#111,344
of 406,425 outputs
Outputs of similar age from Melanoma Research
#2
of 8 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 1,128 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 406,425 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 6 of them.
