Comparison of the effect of different immunological adjuvants on the antibody and T-cell response to immunization with MUC1-KLH and GD3-KLH conjugate cancer vaccines.
While the importance of immunological adjuvants for optimal induction of antibody and T-cell responses against tumor antigens is clear, the relevant potency of different adjuvants is not clear. We have screened 19 different immunological adjuvants with KLH conjugate vaccines containing the two human cancer antigens (MUC1 peptide and GD3 ganglioside) in the mouse. ELISA assays for IgM and IgG antibody responses as well as proliferation and cytokine release (IFN-gamma and IL-4) for T-cell responses were performed. Six adjuvants stood out as being especially effective for induction of IgM and IgG antibodies against both MUC1 and GD3: QS-21, TiterMax, MoGM-CSF, MPL/DETOX and CpG ODN. Of these QS-21, MPL/DETOX and MoGM-CSF were uniformly effective at inducing potent proliferation and potent IFN-gamma and IL-4 responses against KLH while TiterMax and CpG ODN generated potent IFN-gamma responses but less potent proliferation or IL-4 release. Overall, as in our previous experience, QS-21 was the most effective adjuvant. There was no clear evidence for induction of T-cell immunity against either GD3 or MUC1 with any of the adjuvants. There was a strong correlation between the antibodies induced against MUC1 and GD3 with different immunological adjuvants and the strength of the IFN-gamma release against KLH. This suggests that the primary role of adjuvants in the context of these conjugate vaccines may be induction of higher levels of T-cell immunity against KLH, which then leads to higher levels antibody against the conjugated antigens.
Kim
S K
SK
Laboratory of Developmental Tumor Vaccinology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York 10021, USA.
Ragupathi
G
G
Musselli
C
C
Choi
S J
SJ
Park
Y S
YS
Livingston
P O
PO
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D016207:Cytokines; D005732:Gangliosides; D018396:Mucin-1; D018074:Vaccines, Conjugate; C026226:ganglioside, GD3; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin