T/Tn immunotherapy avoiding immune deviation

Abstract

Tumor immunotherapy, capable of inducing both cellular and humoral immune responses, is an attractive treatment strategy for cancer. It has been reported that the inactivation of cell-mediated immunity by hyper-activation of humoral immunity-referred to as immune deviation-does not inhibit tumor growth. We investigated the ability of several adjuvants to elicit Thomsen-Friedenreich (T/Tn)-specific humoral immunity while avoiding immune deviation and conferring protection against tumorigenesis. T/Tn (9:1) antigen was purified from blood type O erythrocytes donated by healthy Korean volunteers. Immunization was performed using T/Tn only, T/Tn mixed with Freund's adjuvant (T/Tn+FA), keyhole limpet hemocyanin (KLH)-conjugated T/Tn mixed with FA (KLH-T/Tn+FA), or oxidized mannan-conjugated T/ Tn mixed with FA (ox-M-T/Tn+FA). Anti-T/Tn antibodies were generated in the T/Tn+FA, KLH-T/Tn+FA, and ox-M-T/ Tn+FA groups. The antibody level was highest in the KLH-T/Tn+FA group. Mice immunized with ox-M-T/Tn+FA showed specific complement-dependent cytotoxicity, and were protected against T/Tn-positive mammary adenocarcinoma cell challenge, although anti-T/Tn antibody levels were the highest in the KLH-T/Tn+FA group. These results demonstrate that an ox-M-conjugated T/Tn vaccine mixed with FA can promote cellular immunity while moderating the humoral immune response, thereby effectively inhibiting tumor growth.

Protective efficacy of a plasmid DNA vaccine against transgene-specific tumors by Th1 cellular immune responses after intradermal injection

“…We also administered two booster injections to re-activate cellular immunity. The immune response to the first immunization was predominantly humoral; however, memory T cells were subsequently recruited to the injection site, which stimulated a Th1-type immune response (Son et al, 2016b). Repeated immunization (boosting) involves dendritic cells (DCs), but it is unclear how frequently booster injections should be administered.…”

“…Cytoplasmic LacZ and transmembrane NIS proteins are translated and retained in cells without being secreted. Moreover, they can be loaded onto major histocopatibility complex class (MHC-)I after translation and onto MHC-II after engulfment by APCs, thereby stimulating helper T cell (Th)1 and Th2 immune responses, and finally avoiding immune deviation (Son et al, 2016b).…”

“…immunizations and the use of non-secreted proteins encoding genes that solve immune deviation (Son et al, 2016b).…”

The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

“…Thus, mucins have been identified as potential prognostic and therapeutic targets for breast cancer development. In fact, vaccines/immunotherapeutic strategies targeting MUC1 have shown promise in pre-clinical animal models and in human clinical trials, with immune cell activation and clinical responses [24,25,42,48,155,156,157,158,159,160,161]. MUC1 is cleaved into N- and C- terminal subunits (MUC1-N and MUC1-C) which form a heterodimeric complex expressed at the cell membrane [162].…”

Profiling of Naturally Occurring Antibodies to the Thomsen-Friedenreich Antigen in Health and Cancer: The Diversity and Clinical Potential

“…Many attempts have been made to induce TF-specific immunity in mice and man [36,95,96]. The TF Abs generated by immunization of mice with T/Tn (9 : 1) purified from blood group O erythrocytes with different adjuvants showed a specific complement-dependent cytotoxicity and protected against the T/Tn-positive mammary adenocarcinoma cell challenge [96]. It has been shown that only TFalpha-specific MAbs and not TFbeta-specific MAbs inhibit the proliferation of epithelial tumor cells [97].…”