ABSTRACT
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. Clinical effects of various grades (complete response, partial response and disease stabilization) with duration of no shorter than 6 months was observed in 25 (41.67%) vaccinated patients. The average survival time of the XPV-treated patients was markedly longer than that of the clinically matched control patients (20 vs. 7 months). The overall 3-year survival rate in the XPV-treated and control group was 16.7% (10 patients) and 0%, respectively. Following a course of ten XPV vaccinations, peripheral blood mononuclear cell (PBMC) proliferation assays revealed increased T-cell immune responses to human Caco-2 colon adenocarcinoma-associated antigens. In addition, relative contents of CD25+ FoxP3+regulatory T-cells in patients with proven immunotherapy-mediated clinical effects (responders) were significantly decreased in the blood, which was paralleled by marked increases in serum levels of proinflammatory cytokines, such as interferon-alpha (IFN-α), IFN-É£, and interleukin-8 (IL-8). Serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-4, and IL-6 were not affected in both responder and non-responder patients. In conclusion, this study provides evidence for the safety, clinical feasibility and immunogenicity of xenogeneic composite cell vaccine administration in colorectal cancer patients. This is the first demonstration that clinical effects of such a vaccine are associated with vaccine-induced, proinflammatory immune responses.
Subject(s)
Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/immunology , Immunity, Cellular/immunology , Immunotherapy, Active/methods , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Heterophile/immunology , Female , Follow-Up Studies , Humans , Male , Melanoma, Experimental/immunology , Mice , Mice, Inbred C57BL , Middle Aged , Treatment OutcomeABSTRACT
The study group included 17 cancer patients, aged 25-55, (stage III-IV), mostly suffering melanoma. All of them received hypnosuggestive therapy to correct psycho-emotional disorders. Significant decrease in anxiety-related indices (p < 0.001) due to therapy pointed to rehabilitation of psychological defenses. Clinical rehabilitation was manifested by improved quality of life (p < 0.01), better habitus and adaptation (p < 0.01). The modulating effect on the macrophageal and phagocytic components of the immune system (p < 0.05) was matched by a significant correlation between psychological defense indices and those of immunological status. Our data have contributed to the existing knowledge about relationships of mind and immunity in cancer patients.
Subject(s)
Neoplasms/immunology , Neoplasms/psychology , Adult , Female , Humans , Hypnosis , Macrophages , Male , Melanoma/immunology , Melanoma/psychology , Middle Aged , Neoplasm Staging , Neoplasms/pathology , Phagocytes , Quality of Life , Skin Neoplasms/immunology , Skin Neoplasms/psychology , Suggestion , ThinkingABSTRACT
Blood-serum concentrations of antibodies to such viruses as herpes simplex virus, cytomegalovirus and Epstein--Barr virus have been assayed versus frequency of viral DNA detection in blood and saliva suspensions from patients with lung and stomach pre-cancers. Condition of local immunity of oral mucosa was assessed on the basis of saliva levels of secretory IgA and lysozyme. It was found that as local immunity of oral mucosa deteriorated, irrespective of pre-cancer localization, high titers of antiviral antibodies (class G) were established. The frequency of herpes DNA was much higher in lymphocytes and cellular sediment from saliva of patients with gastric pre-cancers. The role of herpes viruses in the pathogenesis of precancerous diseases and malignances is discussed.
Subject(s)
Bronchitis/virology , Cytomegalovirus/isolation & purification , Gastritis, Atrophic/virology , Herpesvirus 4, Human/isolation & purification , Mouth Mucosa/virology , Precancerous Conditions/virology , Simplexvirus/isolation & purification , Antibodies, Viral/blood , Bronchitis/immunology , Chronic Disease , Cytomegalovirus/genetics , Cytomegalovirus/immunology , DNA, Viral/blood , Gastritis, Atrophic/immunology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/immunology , Humans , Lymphocytes/immunology , Lymphocytes/virology , Mouth Mucosa/immunology , Precancerous Conditions/immunology , Saliva/immunology , Saliva/virology , Simplexvirus/genetics , Simplexvirus/immunologyABSTRACT
Tritium planigraphy allows one to determine the sterical accessibility of protein hydrocarbon fragments (CH, CH2, CH3 groups) for interaction with tritium atoms on condition of direct transit of the bombarding particles. Using lysozyme as a test system, it was shown to be possible to use these data for the description of protein accessible surface area in terms defined by Lee and Richards. The best agreement between experimental and theoretical results was achieved for an effective radius of the testing probe of 0.9 A. Coefficients were obtained that allowed calculation of the accessibility of amino acid residue as a whole using data about its hydrocarbon fragment accessibility.
