Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors.
BACKGROUND
Dendritic cells (DCs) are the most effective antigen-presenting cells. In the last decade, the use of DCs for immunotherapy of cancer patients has been vastly increased. High endocytic capacity together with a unique capability of initiating primary T-cell responses have made DCs the most potent candidates for this purpose. Although DC vaccination occasionally leads to tumor regression, clinical efficacy, and immunogenicity of DCs in clinical trials has not been yet clarified. The present study evaluated the safety and effectiveness of tumor-lysate loaded DC vaccines in advanced colorectal cancer (CRC) patients with carcinoembryonic antigen (CEA) positive tumors.


RESULTS
Six patients HLA-A*0201-positive were vaccinated with autologous DCs loaded with tumor lysates (TL) together with tetanus toxoid antigen, hepatitis B, and influenza matrix peptides. Two additional patients were injected with DCs that were generated from their sibling or parent with one haplotype mismatch. All patients received the vaccines every 2 weeks, with a total of three intra-nodal injections per patient. The results indicated that DC vaccination was safe and well tolerated by the patients. Specific immune responses were detected and in some patients, transient stabilization or even reduction of CEA levels were observed. The injection of haplotype mismatched HLA-A*0201-positive DCs resulted in some enhancement of the anti-tumor response in vitro and led to stabilization/reduction of CEA levels in the serum, compared to the use of autologous DCs.


CONCLUSIONS
Altogether, these results suggest that TL-pulsed DCs may be an effective vaccine method in CRC patients. Elimination of regulatory mechanisms as well as adjustment of the vaccination protocol may improve the efficacy of DC vaccination.
Tamir
Ayala
A
Department of Immunology, Imperial College at Hammersmith Hospital, London, UK.
Basagila
Ernesto
E
Kagahzian
Arash
A
Jiao
Long
L
Jensen
Steen
S
Nicholls
Joanna
J
Tate
Paul
P
Stamp
Gordon
G
Farzaneh
Farzin
F
Harrison
Phillip
P
Stauss
Hans
H
George
Andrew J T
AJ
Habib
Nagy
N
Lechler
Robert I
RI
Lombardi
Giovanna
G
D000368:Aged; D000951:Antigens, Neoplasm / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen