Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune responses in colorectal carcinoma patients vaccinated with recombinant CEA and granulocyte/macrophage colony-stimulating factor.
Previous studies have indicated that carcinoembryonic antigen (CEA) might be a suitable immunotherapeutic target in colorectal carcinoma (CRC). The aim of the present study was to analyze the immunological and clinical effects of vaccination with CEA together with the adjuvant granulocyte/macrophage colony-stimulating factor (GM-CSF).



Twenty-four resected CRC patients without macroscopic disease were immunized seven times with recombinant CEA at four different dose levels over a 12-month period. Half of the patients received GM-CSF (80 microg/day for 4 consecutive days) at each immunization. Patients were monitored immunologically for 36 months and clinically for 76 months. T-cell response was evaluated by a [(3)H]thymidine incorporation assay, and IgG response was determined by ELISA.



Minor local side effects were common. All 12 patients (100%) in the GM-CSF group developed a CEA-specific T-cell as well as an IgG response. The corresponding figures in the CEA alone group were 9 of 12 (75%) and 8 of 12 (66%), respectively. GM-CSF significantly augmented the amplitude of the T-cell response and the IgG titers. No dose-response relationship was noted. The immune responses at 12 months persisted 24 months after the last vaccination. Anti-CEA IgG titers were associated with increased survival (P < 0.05), whereas standard prognostic factors had no relationship, with the exception of serum CEA value.



Vaccination with recombinant CEA and GM-CSF appears to be a nontoxic regimen inducing potent and durable antigen-specific IgG and T-cell response. The results of this study justify more extensive trials with recombinant CEA protein for immunotherapy of CRC.
Ullenhag
Gustav J
GJ
Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University Hospital, Uppsala, Sweden.
Frödin
Jan-Erik
JE
Jeddi-Tehrani
Mahmood
M
Lidströmer
Niklas
N
Department of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden
Strigård
Karin
K
Eriksson
Emma
E
Samanci
Ali
A
Choudhury
Aniruddha
A
Nilsson
Bo
B
Rossmann
Eva D
ED
Mosolits
Szilvia
S
Mellstedt
Håkan
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000737:chemistry; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D000906:Antibodies; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor