The metastatic form of Melanoma has a reported ten-year survival rate of approximately 15%. Clinical trials have shown modest success in a subset of patients. Particularly, combinational therapy using checkpoint blockade has shown the most success, but many patients do not respond. The patients that do respond to treatments often have a pre-existing antitumor immunity. To generate an optimal anti-tumor immune response, we have previously created a dendritic cell (DC) based adenovirus vaccine targeted against three common melanoma associated antigens: Tyrosinase, MART-1, and MAGE-A6 (TMM2). The vaccine was used in a Phase 1 clinical trial (NCT01622933) , where 35 patients were enrolled. Immature DC (iDC) were generated from patient monocytes (GM-CSF + IL-4), matured (mDC) using IFNG + LPS, and transduced with the adenovirus vaccine (AdVTMM2 DC). Patients received three intradermal injections of the vaccine over the course of one month. Human genome RNA microarray was used to analyze the gene expression profiles of the DC vaccine for each patient.
Overall design
34/35 patient DCs were analyzed for each DC subtype (iDC, mDC, AdVTMM2 DC) using the Affymetrix Human Gene 2.0 ST Array. We investigated gene expression profiles that correlated with overall survival and favorable clinical outcomes in late-stage melanoma patients.
Clinical outcome definitions: PD: Progressive Disease SD: Stable Disease NED1: No Evidence of Disease at time of enrollment and remained NED for ≤ 18 months NED2: No Evidence of Disease at time of enrollment and remained NED for ≥ 18 months PR: Partial Responder (RECIST)
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