Anti-cancer immunoprotective effects of immunization with hydatid cyst wall antigens in a non-immunogenic and metastatic triple-negative murine mammary carcinoma model.

Cancer vaccines have gained lots of attention as the future of cancer treatment. However, poor immunogenicity of tumor-associated antigens often fails to induce an efficient immune response against the tumor. Strange anti-tumor immune responses at the parasite-infected patients due to cross-reactivity have been reported in various studies. Therefore, parasite antigens with significant immunogenicity and high epitope homology with cancer antigens may activate a strong immune response against cancer cells. Herein, the sera of immunized rabbits with the hydatid cyst wall (HCW) antigens were incubated with 4 T1 mammary carcinoma cells to investigate cross-reactivity between the HCW antigens antisera and surface antigens of the breast cancer cells. Also, the SDS-PAGE profile of HCW antigens was prepared and incubated with the breast cancer patients' sera and considerable reactivity was observed between their sera and a specific band (~27/28 kDa) according to Western blotting analyzes. Then, the protein bands with cross-reactivity with breast cancer patients' sera were utilized for prophylactic immunizations of Balb/c mice. The immunoprotective effect of immunization with the HCW antigens caused significant inhibition of 4 T1 breast tumor growth, decrease of metastasis, and enlargement of the tumor-bearing mice survival time in comparison with PBS and pure immune adjuvant injected groups. Mass spectrometry analysis showed that the ~ 27/28 kDa band has numbers of proteins/polypeptides with a high degree of homology with cancer cells antigens which can be the reason for this cross-reactivity and anti-tumor immune response. Taking together, immunization with HCW antigens would be a promising approach in cancer immunotherapy after further investigations.

Immunization with Hydatid Cyst Wall Antigens Can Inhibit Breast Cancer through Changes in Serum Levels of Th1/Th2 Cytokines.

BACKGROUND: Hydatid cysts are the larval stage of Echinococcus granulosus, which lead to humoral and cellular immune responses in hosts. Such immune responses play a key role in the inhibition of tumor growth and cancers. To test this hypothesis, it was attempted not only to examine the changes in serum level of some Th1 and Th2 cytokines but also to find relationships between the cytokines and cancer in 4T1 breast cancer-bearing mice immunized with hydatid cyst wall (HCW) antigens. METHODS: Six to eight-week-old Balb/c female mice were immunized with alum, PBS and HCW antigens, including crude extract of HCW (laminated layer) 28 and 27 kDa protein bands (upper and lower bands) and then challenged with 4T1 breast cancer cells. The amounts of IL2, TNF-α, IFN-γ (Th1 cytokines), and IL4 (Th2 cytokine) were estimated using ELISA. Correlations between these cytokines and cancer parameters (tumor growth, metastasis, and survival) were determined by Pearson's correlation coefficients. RESULTS: Overall, HCW antigens increased the amounts of IL2, TNF-α, IFN-γ, and IL4. Pearson's correlation coefficients indicated reverse relationships between changes in amounts of these cytokines and tumor growth/metastasis. However, except for IL-4, all cytokines had a direct relationship with mouse survival. CONCLUSIONS: The results of this study indicated that the inhibition of breast tumor growth and metastasis and improvement of survival in 4T1 mice immunized with HCW antigens, especially laminated layer and 27 kDa protein band can occur through a rise in the levels of cytokines.

Anti-Toxoplasma gondii antibodies attach to mouse cancer cell lines but not normal mouse lymphocytes.

Toxoplasma gondii (T. gondii) is prevalent intracellular parasite and a cause of worldwide infection in the human population. An inhibitory effect of this parasite on cancer growth has been demonstrated in cell culture and animal models. To determine whether the anticancer activities of T. gondii are associated with host immune response, in the current study the reactivity of anti-T. gondii antiserum with the surface of cancer cell lines was investigated. Anti-T. gondii antibodies were raised in rabbit and the reaction of this antiserum in comparison with other anti-parasite antisera (anti-T. vaginalis, anti-hydatid cyst fluid, anti-protoscolices antigens) with mouse melanoma or breast cancer cells lines was investigated using flow cytometry. Anti-T. gondii antiserum reacted markedly with the surface of mouse melanoma and breast cancer cells, and less so with the normal mouse spleen lymphocytes. Meanwhile, the other anti-parasite antisera did not react strongly with the surface of cancer cells compared with normal mouse spleen lymphocytes. In summary, it has been demonstrated herein that anti-T. gondii antiserum may selectively react with the surface of mouse cancer cells but not with normal mouse spleen lymphocytes. Therefore, further study on anti-Toxoplasma antibodies may be useful for directing the application of selective drug delivery in cancer treatment.

Therapeutic effect of acupuncture in BALB/c model of cutaneous leishmaniasis.

BACKGROUND: Current research findings demonstrate that acupuncture, a traditional Chinese medicine, has beneficial effects on several acute and chronic infectious and inflammatory diseases. Acupuncture promotes tissue healing and regulates immune response in various disease conditions. Cutaneous leishmaniasis (CL) is a parasitic disease caused by protozoan from genus Leishmania. Acupuncture is supposed to accelerate healing of CL because of common mechanisms involved in the cure of the CL lesions. MATERIALS AND METHODS: 60 BALB/c mice were experimentally infected with L. major strain MRHO/IR/75/ER and divided into three groups: (1) Treatment group received acupuncture 2 times a week for 5 weeks (10 sessions) with intraperitoneal diazepam as a sedative agent. (2) Diazepam control group only received diazepam the same as the treatment group. (3) Control group did not receive any intervention. Size of the lesions was measured before the experiment, on session 5 and 10 and 4 weeks after the experiment. Parasite burden was evaluated by microscopic assay as well as quantitative real-time polymerase chain reaction technique. RESULTS: Size of the lesions decreased significantly on session 5 in treated group in comparison with session 0 (P = 0.02) while the size of the lesions increased significantly in two control groups on session 5 and 4 weeks after treatment (P = 0.04 and P = 0.01 respectively). Mean parasite burden did not show a significant difference between or within groups on session 0 and 10 by any methods. CONCLUSIONS: This investigation showed that acupuncture decreased size of the CL lesions by session 5 in the BALB/c mice model, but did not cause a significant reduction in parasite burden.