The biological effects of syngeneic and allogeneic cytokine-expressing prophylactic whole cell vaccines and the influence of irradiation in a murine melanoma model.
Allogeneic whole tumour cell vaccines are inherently practical compared with autologous vaccines. Cell lines are derived from allogeneic tumour, grown in bulk and then administered as a vaccine to the patient, following irradiation, which not only prevents any replication but also enhances antigen presentation. Protection is believed to occur through the presentation of antigens shared between the syngeneic and allogeneic tumours. Although cytokine-transfected tumour whole cell vaccines have been used clinically, little data is available comparing the effects of immunomodulatory cytokine-transfection directly on the same cells when used as both an allogeneic and autologous vaccine. To address this, weakly immunogenic B16-F10 (H-2b) murine melanoma was transfected to secrete either GM-CSF, IL-4 or IL-7. Prophylactic vaccination of both syngeneic C57/BL6 (H-2b) (B6) and allogeneic C3H/Hej (H-2k) (C3H) mice showed the effects of transfected cytokine varied between models. Both GM-CSF and IL-7 significantly (P<0.05) increased the levels of protection within syngeneic B6 mice, but had a diminished effect (P>0.05) within C3H allogeneic mice. Allogeneic B16-F10 cells and syngeneic K1735 cells generated CTL against K1735 suggesting cross-reactive immunity. Using cells labeled with fluorescent dye we demonstrate that irradiated vaccines, of either syngeneic or allogeneic origin, appear to generate potent immune responses and fragments of either vaccine remain at the injection site for up to 9 days. This study shows that protection can be enhanced in vivo by using transfected cytokine, but suggests that irradiated whole cell vaccines, of either tissue-type, are rapidly processed. This leads to the conclusion that the cytokine effects are transient and thus transfection with cytokine may be of limited long-term use in situ.
Labarthe
Marie-Christine
MC
Onyvax Ltd, St George's Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 ORE, UK.
Halanek
Nicole
N
Birchall
Lindsay
L
Russell
Nick
N
Desel
Christiane
C
Todryk
Stephen
S
Peters
Marcus J
MJ
Lucas
Aisha
A
Falkenberg
Frank W
FW
Dalgleish
Angus G
AG
Whelan
Mike
M
Ward
Stephen John
SJ
D000818:Animals; D019496:Cancer Vaccines / Q000528:radiation effects*; D017690:Cell Transplantation; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D008546:Melanoma, Experimental / Q000517:prevention & control*; D051379:Mice; D009368:Neoplasm Transplantation; D014162:Transfection; D014184:Transplantation, Homologous / Q000276:immunology*; D014185:Transplantation, Isogeneic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D016207:Cytokines