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1.
J Transl Med ; 22(1): 657, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010088

ABSTRACT

BACKGROUND: The combination of immune checkpoint inhibitors with radiotherapy can enhance the immunomodulation by RT and reduce the growth of distant unirradiated tumors (abscopal effect); however, the results are still not very satisfactory. Therefore, new treatment options are needed to enhance this effect. Our previous study showed that the combination of Bifidobacterium (Bi) and its specific monoclonal antibody (mAb) could target and alleviate hypoxia at the tumor site and act as a radiosensitizer. In this study, we explored the anti-tumor efficacy of quadruple therapy (Bi + mAb and RT + αPD-1). The current study also aimed to probe into the complex immune mechanisms underlying this phenomenon. METHODS: Constructed 4T1 breast and CT26 colon cancer tumor models. A comprehensive picture of the impact of constructed quadruple therapy was provided by tumor volume measurements, survival analysis, PET/CT imaging, immune cell infiltration analysis and cytokine expression levels. RESULTS: The abscopal effect was further amplified in the "cold" tumor model and prolonged survival in tumor-bearing mice. Bi can colonized in primary and secondary tumors and direct the mAb to reach the tumor site, activate complement, enhance the ADCC effect and initiate the innate immune response. Then combined with αPD-1 and radiotherapy to stimulate adaptive immune response and synergize with cytokines to expand the immune efficacy and generate effective anti-tumor immune response. CONCLUSIONS: Bi was used as an artificially implanted anaerobic target to cause a transient "infection" at the tumor, causing the tumor to become locally inflamed and "hot", and at the same time, mAb was used to target Bi to enhance the local immune effect of the tumor, and then combined with radiotherapy and αPD-1 to amplify the abscopal effect in multiple dimensions. Therefore, the present study provided a new idea for the multipotent immune-activating function of antibody-targeted anaerobic bacteria for the RT treatment of extensively metastasized cancer patients.


Subject(s)
Antibodies, Monoclonal , Mice, Inbred BALB C , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/pharmacology , Cell Line, Tumor , Female , Bacteria, Anaerobic/immunology , Mice , Bifidobacterium , Cytokines/metabolism , Positron Emission Tomography Computed Tomography , Neoplasms/radiotherapy , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/therapy , Combined Modality Therapy
2.
Heliyon ; 9(7): e17910, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37501973

ABSTRACT

Background: Retroauricular injection is a local steroid hormone administration method commonly used to treat deafness or tinnitus. The acute stage of Bell's Palsy is an acute disease that requires steroid therapy. Retroauricular injection may replace oral administration of steroid hormones in the treatment of this disease as well as reduce the occurrence of adverse reactions. Methods: This study included patients with Bell's Palsy within seven days of onset. A total of 120 patients were enrolled as the study subjects and randomly divided into two groups: the experimental group and the control group. Both groups received routine acupuncture treatment and took a traditional Chinese medicine decoction corresponding with the syndrome type. Methylprednisolone sodium succinate was injected into the bone surface of retroauricula in the experimental group, and prednisone acetate was orally administered in the control group. The main outcome indicators were the House-Brackmann (HB) grade, the facial disability index (FDI), and time of postauricular pain after one month of treatment. Results: There were no significant differences in the HB grade (2.00 ± 1.06 vs. 1.88 ± 1.06, P=), FDIP (97.25 ± 6.00 vs. 97.17 ± 7.39, P=), and FDIS (0.60 ± 3.02 vs. 1.33 ± 4.27, P=) at 30 days after treatment between the two groups (P > 0.05). Postauricular pain disappeared earlier in the experimental group (3.66 ± 1.67 days) than in the control group (6.31 ± 2.34); the difference was statistically significant (P ≤ 0.001). The adverse reaction rate was lower in the experimental group (15.00%) than in the control group (21.66%). Interpretation: Although the dose of steroid hormone injected into the bone surface of retroauricula in the treatment of Bell's Palsy is lower than the administered dose of oral hormones, it has the same curative effect; however, it has a better effect regarding to the duration of postauricular pain and adverse reactions.

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