A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates
We recently reported the clinical results of a Phase I trial combining ipilimumab with a vaccine containing transgenes for prostate-specific antigen (PSA) and for a triad of costimulatory molecules (PROSTVAC) in patients with metastatic castration-resistant prostate cancer. Thirty patients were trea...
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Published in | Cancer Immunology, Immunotherapy Vol. 63; no. 4; pp. 407 - 418 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.04.2014
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | We recently reported the clinical results of a Phase I trial combining ipilimumab with a vaccine containing transgenes for prostate-specific antigen (PSA) and for a triad of costimulatory molecules (PROSTVAC) in patients with metastatic castration-resistant prostate cancer. Thirty patients were treated with escalating ipilimumab and a fixed dose of vaccine. Of 24 chemotherapy-naïve patients, 58 % had a PSA decline. Combination therapy did not exacerbate the immune-related adverse events associated with ipilimumab. Here, we present updated survival data and an evaluation of 36 immune cell subsets pre- and post-therapy. Peripheral blood mononuclear cells were collected before therapy, at 13 days and at 70 days post-initiation of therapy, and phenotyped by flow cytometry for the subsets of T cells, regulatory T cells, natural killer cells, and myeloid-derived suppressor cells. Associations between overall survival (OS) and immune cell subsets prior to treatment, and the change in a given immune cell subset 70 days post-initiation of therapy, were evaluated. The median OS was 2.63 years (1.77–3.45). There were trends toward associations for longer OS and certain immune cell subsets before immunotherapy: lower PD-1
+
Tim-3
NEG
CD4
EM
(
P
= 0.005, adjusted
P
= 0.010), higher PD-1
NEG
Tim-3
+
CD8 (
P
= 0.002, adjusted
P
= 0.004), and a higher number of CTLA-4
NEG
Tregs (
P
= 0.005, adjusted
P
= 0.010). We also found that an increase in Tim-3
+
natural killer cells post- versus pre-vaccination associated with longer OS (
P
= 0.0074, adjusted
P
= 0.015). These results should be considered as hypothesis generating and should be further evaluated in larger immunotherapy trials. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Both authors contributed equally. |
ISSN: | 0340-7004 1432-0851 |
DOI: | 10.1007/s00262-014-1524-0 |