Research on programmed-death 1 (PD-1) found on T cells and its receptor, programmed-death ligand 1 (PD-L1), found in varying levels on tumor is a central topic in immunotherapy. However, comparatively little research has been done on the soluble version of the protein (sPD-1) found in blood plasma.
Now a new study, published in the journal Oncotarget,1has assessed sPD-1 levels in patients with metastatic melanoma, before and after treatment with patient-specific autologous cancer vaccines.
“Probably 99% of the papers on PD-1 revolve around PD-1 expressed on the surface of T cells; this sPD-1 variant has been basically ignored in the meantime. It’s a very understudied area,” said Eric Bartee, PhD, associate professor in the department of microbiology and immunology at the Medical University of South Carolina, Charleston.
The research came from a phase 2 trial that was a randomized trial comparing autologous dendritic cell vaccines (DCV) and autologous tumor cell vaccines (TCV) for the treatment of metastatic melanoma (ClinicalTrials.gov Identifier: NCT00948480).2 In that trial, 22 patients were treated with TCV and 17 with DCV, with the study finding a survival improvement in DCV-treated patients compared with TCV-treated individuals.
“We saw a survival difference between the 2 therapies and looked at biomarkers that might explain this and also the mechanism of action,” said Robert Dillman, MD, chief medical officer at AIVITA Biomedical Inc., Irvine, California, and senior author of the study.
sPD-1 was assayed by an ELISA assay at week 0, a week before the first of 3 subcutaneous injections of therapy and at week 4, a week after the third injection.
“sPD-1 was one of the biomarkers involved in the study and the one that came the closest with association with outcome for DCV-treated patients,” added Dr Dillman.
Notably, patients had a huge range of detectable sPD-1 at week 0 with detectable amounts from 1 pg/mL to more than 500,000 pg/mL. However, these baseline levels were not found to be prognostic for survival.