A novel dendritic cell-based cancer vaccine produces promising results in a syngenic CC-36 murine colon adenocarcinoma model.
BACKGROUND
This study was conducted to test the efficacy of a new cancer vaccine, composed of dendritic cells (DCs) pulsed with an interleukin-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) in a CC-36 murine colon adenocarcinoma model.


METHODS
CC-36 tumor cells were injected subcutaneously into the left flank of four- to six-week old male BALB/c mice. The mice were divided into three groups, each of which received one of the following treatments: (1) DCs pulsed with the IL-2 gene-encoded vaccinia oncolysate (DC-IL-2VCO), (2) DCs pulsed with the tumor oncolysate alone (DC-CO), or (3) no treatment (control). Tumor incidence was measured, and survival rates were compared using a paired Student's t-test. Cytolytic T cell activity was measured in peripheral blood lymphocytes (PBL) and splenic lymphocytes using a (51)Cr-release assay. Lastly, mice were depleted of either CD4+ or CD8+ lymphocytes prior to receiving the vaccine to test the mechanism of tumor immunity in these mice.


RESULTS
Mice treated with DC-IL-2VCO demonstrated decreased tumor burden, increased survival, and greater cytolytic activity compared with control mice and mice receiving DC-CO. In addition, mice depleted of CD8+ T cells prior to immunization with IL-2VV + DC-IL-2VCO had a significant increase in the incidence of tumor, similar to the untreated control mice.


CONCLUSIONS
DCs pulsed with an IL-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) produced safe and effective immune responses in a murine CC-36 colon adenocarcinoma model. This vaccine (DC-MelVac; Patent no. 11221/5) has the potential to treat humans with cancer, and has received FDA approval for use in Phase I clinical trials.
Jack
Angela M
AM
Surgery Research Laboratory, Department of Surgery, Saint Vincent's Catholic Medical Centers/New York Medical College, New York, NY 10029, USA.
Aydin
Nebil
N
Montenegro
Grace
G
Alam
Khorshed
K
Wallack
Marc
M
D000230:Adenocarcinoma / Q000453:epidemiology / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D019496:Cancer Vaccines / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D015994:Incidence; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D047368:Tumor Burden; D014616:Vaccinia virus / Q000235:genetics
D019496:Cancer Vaccines; D007376:Interleukin-2