Total threshold cytotoxicity of therapeutic antibodies for selective destruction of pathogenic memory T cells: implications for immunotherapy of autoimmune and allergenic disorders.

: Pathogenic memory CD4 T cells are the mainspring of autoimmune and allergic disorders, suggesting that effective pathogenetic immunotherapy should be primarily directed onto their direct inactivation without affecting normal cells. : A novel immunotherapeutic concept is proposed that applies suboptimal doses of several cytotoxic antibodies (Abs) against membrane antigens (Ags) (such as CD4, СD45RO, СD69, CD103, CD27, CD38, DR, etc.) with a view to achieve a threshold density of immune complexes on pathogenic memory CD4 T cells for their selective elimination.

Attaining threshold antibody cytotoxicity for selective tumor cell destruction: an opinion article.

We propose a novel immunotherapeutic paradigm that justifies application of several antibodies to various membrane-associated antigens to achieve a critical threshold density of immune complexes on the surface of cancer cells sufficient for triggering downstream cytolytic pathways. Indeed, some cancer-associated antigens (such as cancer/testis antigens) were found to be expressed on many cancer (but not normal) cells, with their baseline membrane expression levels being originally quite low for some of them, or even further down-regulated due to immune-driven cell selection. To achieve the mandatory threshold density of membrane-associated immune complexes on malignant cells, the concept stipulates combined application of antibodies specific for a cancer-associated antigen along with antibodies against an antigen expressed not only on tumor, but also on normal cells.

Xenogeneic cell-based vaccine therapy for colorectal cancer: Safety, association of clinical effects with vaccine-induced immune responses.

An accumulating body of evidence suggests that xenogeneic vaccines can be very effective in breaking the immune tolerance to human tumor-associated antigens (TAAs). We assessed adverse effects, as well as clinical and immune responses induced by a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells in 60 stage IV colorectal cancer patients. Neither grade III/IV toxicities, nor laboratory and clinical signs of systemic severe autoimmune disorders were documented in any XPV-treated patient.

Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits.

New therapies for melanoma have yielded promising results, but their application is limited because of serious side-effects and only moderate impact on patient survival. Vaccine therapies may offer some hope by targeting tumor-specific responses, considering the immunogenic nature of melanomas. To investigate the safety profile and efficiency of a xenogeneic cell-based vaccine therapy in stage III melanoma patients and evaluate the survival rate in treated patients.

Multiple-purpose immunotherapy for cancer.

Anti-cancer vaccination is a useful strategy to elicit antitumor immune responses, while overcoming immunosuppressive mechanisms. Whole tumor cells or lysates derived thereof hold more promise as cancer vaccines than individual tumor-associated antigens (TAAs), because vaccinal cells can elicit immune responses to multiple TAAs. Cancer cell-based vaccines can be autologous, allogeneic or xenogeneic.

Clinically feasible approaches to potentiating cancer cell-based immunotherapies.

The immune system exerts both tumor-destructive and tumor-protective functions. Mature dendritic cells (DCs), classically activated macrophages (M1), granulocytes, B lymphocytes, aβ and ɣδ T lymphocytes, natural killer T (NKT) cells, and natural killer (NK) cells may be implicated in antitumor immunoprotection. Conversely, tolerogenic DCs, alternatively activated macrophages (M2), myeloid-derived suppressor cells (MDSCs), and regulatory T (Tregs) and B cells (Bregs) are capable of suppressing antitumor immune responses.

A balance between tissue-destructive and tissue-protective immunities: a role of toll-like receptors in regulation of adaptive immunity.

The immune system has been shown to be involved in not only the host defense against infectious pathogens but also in tissue repair processes continuously occurring in the body. Our review presents the hypothesis about the mechanism of TLR-mediated regulation of adaptive immune responses linked to the tissue destruction. In our opinion following injury to a tissue, the expression of tissue-specific determinant/MHC class II complexes on dendritic cells and macrophages are upregulated significantly due to the increased uptake of tissue debris.