Therapy With Carboplatin and Anti-PD-1 Antibodies Before Surgery Demonstrates Sustainable Anti-Tumor Effects for Secondary Cancers in Mice With Triple-Negative Breast Cancer

Abstract

Patients with triple-negative breast cancer (TNBC) suffer an unfavorable prognosis. Carboplatin (CBDCA) as a cytotoxic reagent has been widely administered to patients with cancer including TNBC. Programmed cell death protein 1 (PD-1) is an immune checkpoint, blockade of which unleashes T cell functions that kill cancer cells. However, the efficacy of CBDCA combined with anti-PD-1 antibodies in TNBC has not been determined. Patient-derived xenografts (PDX) were implanted to immune-deficient mice. Three mouse TNBC cell lines (4T1, EMT6, and E0771) were seeded to immune-competent mice. Tumor volumes and survival rates were monitored. CBDCA and anti-PD-1 antibodies were administered by intra-peritoneal injection at designated time points. Total CD8 + T cells, memory CD8 + T cells, and CD103 + dendritic cells (DC) in the tumor were measured by flow cytometry. Tumor-specific CD8 + T cells were quantified by the ELISpot assay. Administration of CBDCA to PDX-bearing mice induced increased levels of tumor cell necrosis and reduced tumor size. Treatment with CBDCA and anti-PD-1 antibodies reduced TNBC tumor volumes and slightly improved survival rates. More importantly, therapy with CBDCA and anti-PD-1 antibodies before surgery showed a remarkably improved, sustainable protection against a secondary tumor after surgery by a CD8 +-T-cell-dependent manner, which required CCL4 expressed in the tumor and subsequently CD103 + DC recruited to the tumor microenvironment. Immunochemotherapy with CBDCA and anti-PD-1 antibodies before surgery improves the outcome of a secondary tumor after surgery via increasing the number of tumor-specific CD8 + T cells in the tumor microenvironment of murine TNBC. These results highlight the possibility to utilize this regimen in clinical practice.

IL-31 induces antitumor immunity in breast carcinoma

“…The PyMT breast carcinoma model is used to study Luminal B breast carcinoma, 29 whereas EMT6 model is considered to be triple negative breast carcinoma. 30 Control cells were stably transduced with empty vector to generate PyMT-ev and EMT6-ev cell lines. Both IL-31-expressing cell lines secreted high levels of IL-31 and exhibited similar proliferation rates in comparison with their counterpart controls (online supplementary figure S2A).…”

Enzyme production ofd-gluconic acid and glucose oxidase: successful tales of cascade reactions

“…377 In the area of cancer therapy, one example of drugcontrolled release using glucose oxidase oxidation of metabolic glucose is the use of anti-PD-1 as a target molecule. 378,379 To achieve this goal, a microneedle was fabricated using hyaluronic acid and with pH-sensitive dextran nanoparticles that encapsulate anti-PD-1 and glucose oxidase. 380 When glucose oxidase converts glucose into D-gluconic acid and the pH decreases, the dextran nanoparticles dissociated and released anti-PD-1 more effectively than from a microneedle without this pH-trigged release or employing the free antibody, using B16F10 mouse melanoma as a model system.…”

Gemcitabine synergizes with cisplatin to inhibit nasopharyngeal carcinoma cell proliferation and tumor growth

“…The tumor volume (TV) was calculated using the formula: TV = ℼ/6 × L×S × H. For mice survival model (n = 10 per group), the survival was determined by sacrificing the mice when tumor reached a volume of 2 cm × 2 cm × 2cm for ethical considerations according to the Guidelines for the Welfare and Use of Animals in Cancer Research. 13,14 For the extraction of tissue total protein, took an appropriate amount of tissue, poured liquid nitrogen into a mortar and grinded it, and then, added an appropriate amount of lysate, continue grinded until the lysate began to melt. Next, aspirated the lysate and tissue homogenate and transferred to a new tube.…”