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Cancer Immunol Immunother. 2016 Nov;65(11):1353-1364. Epub 2016 Aug 31.

A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-α-2b in patients with CEA-expressing carcinomas.

Author information

1
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
2
National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA.
3
Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD, USA.
4
Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.
5
Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
6
Division of Surgical Oncology, The Ohio State University, N924 Doan Hall, 410 W. 10th Avenue, Columbus, OH, 43210, USA. william.carson@osumc.edu.

Abstract

Prime-boost vaccination with recombinant (r) vaccinia(V)-CEA(6D)-TRICOM (triad of co-stimulatory molecules B7.1, ICAM-1 and LFA-3) and rFowlpox(F)-CEA(6D)-TRICOM infect antigen-presenting cells and direct expression of co-stimulatory molecules. We hypothesized that co-administration of vaccine with GM-CSF and interferon alpha (IFN-α) would have efficacy in CEA-expressing cancers. Patients with CEA-expressing cancers received the rV-CEA(6D)-TRICOM vaccine subcutaneously (s.c.) on day 1 followed by GM-CSF s.c. to the injection site on days 1-4. In Cycle 1, patients received thrice weekly s.c. injections of IFN-α-2b the week after rV-CEA(6D)-TRICOM. In Cycles 2-4, patients received thrice weekly s.c. injections of IFN-α-2b the same week that rF-CEA(6D)-TRICOM was given. The first cohort received no IFN followed by dose escalation of IFN-α in subsequent cohorts. Thirty-three patients were accrued (mean 59.8 years). Grade 3 toxicities included fatigue and hyperglycemia. Grade 4-5 adverse events (unrelated to treatment) were confusion (1), elevated aspartate transaminase (AST)/alanine transaminase (ALT) (1), and sudden death (1). No patients had a partial response, and eight patients exhibited stable disease of ≥3 months. Median progression-free survival and overall survival (OS) were 1.8 and 6.3 months, respectively. Significantly higher serum CD27 levels were observed after vaccine therapy (p = 0.006 post 1-2 cycles, p = 0.003 post 3 cycles, p = 0.03 post 4-7 cycles) and 42 % of patients assayed developed CEA-specific T cell responses. Pre-treatment levels of myeloid-derived suppressor cells correlated with overall survival (p = 0.04). Administration of IFN-α led to significantly increased OS (p = 0.02) compared to vaccine alone. While the vaccine regimen produced no clinical responses, IFN-α administration was associated with improved survival.

KEYWORDS:

Carcinoembryonic antigen (CEA); Colorectal cancer; Immunotherapy; Interferon alpha-2b; Vaccines

PMID:
27581603
PMCID:
PMC5071149
DOI:
10.1007/s00262-016-1893-7
[Indexed for MEDLINE]
Free PMC Article

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