Oncotarget

Research Papers:

Preliminary observations on soluble programmed cell death protein-1 as a prognostic and predictive biomarker in patients with metastatic melanoma treated with patient-specific autologous vaccines

Robert O. Dillman _, Gabriel I. Nistor, Bryce T. McLelland, Candace Hsieh, Aleksandra J. Poole, Andrew N. Cornforth and Hans S. Keirstead

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Oncotarget. 2019; 10:5359-5371. https://doi.org/10.18632/oncotarget.27164

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Abstract

Robert O. Dillman1,2, Gabriel I. Nistor1, Bryce T. McLelland1, Candace Hsieh1, Aleksandra J. Poole1, Andrew N. Cornforth2 and Hans S. Keirstead1

1 AIVITA Biomedical, Inc. Irvine, CA 92612, USA

2 Hoag Cancer Institute, Newport Beach, CA 92663, USA

Correspondence to:

Robert O. Dillman,email: robert.dillman55@gmail.com

Keywords: programmed cell death protein -1 (PD-1); dendritic cell vaccines; metastatic melanoma

Received: May 23, 2019     Accepted: August 05, 2019     Published: September 03, 2019

ABSTRACT

Because of its role as an immune checkpoint, levels of soluble programmed cell death protein-1 (sPD-1) could be useful as a prognostic biomarker or predictive biomarker in cancer patients treated with vaccines. Very low levels of sPD-1 may indicate lack of an existing anti-cancer immune response; very high levels may indicate an active immune response that is suppressed. In between these extremes, a decrease in PD-1 following injections of an anti-cancer vaccine may indicate an enhanced immune response that has not been suppressed. Blood samples obtained during a randomized trial in patients with metastatic melanoma were tested from 22 patients treated with a tumor cell vaccine (TCV) and 17 treated with a dendritic cell vaccine (DCV). Survival was better in DCV-treated patients. sPD-1 was measured at week-0, one week before the first of three weekly subcutaneous injections, and at week-4, one week after the third injection. The combination of a very low baseline sPD-1, or absence of a very high PD-1 at baseline followed by a decline in sPD-1 at week-4, was predictive of surviving three or more years in DCV-treated patients, but not TCV-treated. Among DCV-treated patients, these sPD-1 criteria appropriately classified 8/10 (80%) of 3-year survivors, and 6/7 (86%) of patients who did not survive three years. These preliminary observations suggest that sPD-1 might be a useful biomarker for melanoma patients being considered for treatment with this DCV vaccine, and/or to predict efficacy after only three injections, but this would have to be confirmed in larger studies.


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