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Local reactivity, biomarkers predict response to autologous melanoma vaccine
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PARIS — The intensity of delayed-type hypersensitivity response predicted better survival among patients with macroscopic stage IIIB-C melanoma who received a vaccine made of dinitrophenyl-coated autologous melanoma cells, according to study results presented at the WIN Symposium.
In addition, patients whose tumors exhibited high expression of biomarkers related to anti-cancer immune response had better prognosis, researchers said.
No proven therapies exist for patients with macroscopic metastases to draining lymph nodes and resectable metastases in-transit, according to background information provided by researchers.
The investigators conducted the study to evaluate OS and DFS in patients who received a vaccine made of DNP-coated autologous melanoma cells, as well as to identify tumor biomarkers associated with improved survival and strong immune response.
The analysis included 116 patients with stage IIIB (n=51) or IIIC (n=65) disease. All patients had undergone complete surgical excision of their tumors, and 48 patients (41%) had undergone additional radiotherapy.
All patients received eight doses of the vaccine, which was comprised of irradiated tumor cells that were derived from resected metastases and then mixed with dinitrophenyl and Bacillus Calmette–Guérin.
Vaccine doses were administered 21 days apart. Investigators evaluated skin response to unmodified autologous melanoma cells during the last vaccination.
The researchers used the C-map assay to conduct gene expression profiling on 35 melanoma cell lines. They then measured 1,000 transcripts to calculate the complete genomic signature, with the intention of analyzing the impact of individual gene expression on OS and intensity of delayed-type hypersensitivity (DTH) as a marker of anti-tumor activity.
Study results showed the intensity of DTH response correlated with survival.
Forty-one patients (35%) demonstrated strong positive DTH, according to researchers. Among those patients, 5-year OS was 73% and 5-year DFS was 66%.
Sixty-eight patients demonstrated weaker DTH. Among those patients, 5-year OS was 41% (P=.003) and 5-year DFS was 33% (P=.015).
Researchers determined osteopontin, a glycoprotein, was the biomarker that most strongly correlated with DTH and prolonged survival. Disease with higher expression of five cancer testis antigens — CTAG2, MAGE-A1, MAGE-A3, SOX and BAGE — also correlated with improved survival, researchers wrote.
"As cancer testis antigens are not markers of favorable prognosis, we suggest that they represent good targets of immunity and that vaccination with a tumor bearing these antigens was more effective and thus more protective," the researchers wrote.
For more information:
Lotem M. Abstract #P6.02. Presented at: WIN Symposium; July 10-12, 2013; Paris.
Disclosure: The researchers report no relevant financial disclosures.