Anti-tumor vaccine efficacy depends on adjuvant type and associates with induced IgG subclass and glycosylation profiles
Lehrian S, Wasynczuk A, Petry J, Guderian M, Nouta J, Buhre J, Lunding H, Köcher P, Schumacher H, Dühring L, Kurwahn K, Manzhula K, Manz R, Bartsch Y, Wuhrer M, Ehlers M
Erschienen in
Experimental Hematology & Oncology: Volume 14, Issue 1, Page 122
Abstract
Vaccination with tumor-(neo) antigen plus adjuvant is emerging as a promising cancer-therapy. However, as different adjuvants induce distinct immune cell and antibody (Ab) responses, selecting the right adjuvants remains challenging. Here, we evaluated the following vaccine adjuvants to promote protection against tumor-growth in mice and correlated IgG subclass and Fc N-glycosylation responses: Alum; the toll-like receptor activators Poly(I:C) and MPLA; Alum-Poly(I:C); and the more inflammatory water-in-oil adjuvants Montanide, IFA, CFA, and M.tb.-enriched (e)CFA. While Alum and Montanide failed to protect, MPLA and IFA tended to protect, and Poly(I:C), Alum-Poly(I:C), CFA, and eCFA significantly protected against tumor-growth. Across all adjuvants, tumor-protection correlated with the induction of highly activating IgG2(c/b) Abs and afucosylated (F0) IgG1 Abs, the latter showing up to 5% abundance. While all adjuvants transiently induced IgG1 F0 following initial immunization, Poly(I:C)- and eCFA-induced memory responses also generated IgG1 F0 after repeated antigen-exposure without adjuvants. Additionally, Poly(I:C)-induced tumor-protection was associated with high IgG2c/IgG1 ratios, high levels of IgG galactosylation and sialylation, and IFNγ-producing CD8 + Tc1-cells. Conversely, Ova-eCFA-induced tumor-protection was additionally associated with high levels of IgG across all subclasses, but low levels of galactosylation and sialylation, and CD8 + Tc17- and CD4 + Th17-cells. Accordingly, tumor protecting adjuvants may induce common but also different protecting programs. A tumor-antigen-specific IgG2a monoclonal (m)Ab protected against tumor-growth in both its de-galactosylated and galactosylated plus sialylated forms, suggesting common and possibly distinct protective mechanisms. Tumor-protection via serum transfer from Poly(I:C)-immunized mice depended more on NK-cells, whereas eCFA-induced and non-sialylated/non-galactosylated mAbs promoted neutrophil activation. These findings may help to improve tumor vaccination protocols.
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