title: 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.
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.
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Megan C
authors: MC
authors: Duggan
authors: National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA.
authors: Caroline
authors: C
authors: Jochems
authors: National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA.
authors: Renee N
authors: RN
authors: Donahue
authors: National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA.|Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD, USA.
authors: Jacob
authors: J
authors: Richards
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Volodymyr
authors: V
authors: Karpa
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Elizabeth
authors: E
authors: Foust
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Bonnie
authors: B
authors: Paul
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Taylor
authors: T
authors: Brooks
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Susheela
authors: S
authors: Tridandapani
authors: Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.
authors: Thomas
authors: T
authors: Olencki
authors: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors: Xueliang
authors: X
authors: Pan
authors: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: Gregory B
authors: GB
authors: Lesinski
authors: National Cancer Institute, Laboratory of Tumor Immunology and Biology, Bethesda, MD, USA.
authors: Jeffrey
authors: J
authors: Schlom
authors: Division of Surgical Oncology, The Ohio State University, N924 Doan Hall, 410 W. 10th Avenue, Columbus, OH, 43210, USA. william.carson@osumc.edu.
authors: William E
authors: WE
authors: Carson Iii
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics; D018968:CD58 Antigens / Q000235:genetics; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018968:CD58 Antigens; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016898:Interferon-alpha; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014614:Vaccines, Synthetic; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Carcinoembryonic antigen (CEA); Colorectal cancer; Immunotherapy; Interferon alpha-2b; Vaccines