Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2-gene encoded vaccinia virus studied in a syngeneic CC-36 murine colon hepatic metastasis model

We have directly compared the efficacy of two immunotherapeutic strategies for the treatment of cancer: “vaccination” of tumor-bearing mice with genetically modified dendritic cells (DCs), and vaccination with genetically modified tumor cells. Using several different preexisting tumor models that make use of B16F10 melanoma cells expressing a target tumor antigen (human melanoma-associated gene [MAGE]-1), we found that vaccination with bone marrow–derived DCs engineered to express MAGE-1 via adenoviral-mediated gene transfer led to a dramatic decrease in the number of metastases in a lung metastasis model, and led to prolonged survival and some long-term cures in a subcutaneous preexisting tumor model. In contrast, vaccination with granulocyte/macrophage colony-stimulating factor (GM-CSF)–transduced tumor cells, previously shown to induce potent antitumor immunity in standard tumor challenge assays, led to a decreased therapeutic effect in the metastasis model and no effect in the subcutaneous tumor model. Further engineering of DCs to express either GM-CSF, tumor necrosis factor α, or CD40 ligand via retroviral-mediated gene transfer, led to a significantly increased therapeutic effect in the subcutaneous tumor model. The immunological mechanism, as shown for GM-CSF–transduced DCs, involves MAGE-1–specific CD4+ and CD8+ T cells. Expression of GM-CSF by DCs led to enhanced cytotoxic T lymphocyte activity, potentially mediated by increased numbers of DCs in draining lymph nodes. Our results suggest that clinical studies involving the vaccination with genetically modified DCs may be warranted.

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A Novel CpG Oligodeoxynucleotide Enhanced the Therapeutic Effect of Epirubicin on Bladder Tumors in Rats

10.21203/rs.3.rs-889443/v1 ◽

2021 ◽

Author(s):

Yang Luo ◽

Xiaoyi Fu ◽

Bin Dong ◽

Hongsheng Men ◽

Shulin Zhang ◽

...

Keyword(s):

Therapeutic Effect ◽

Rat Model ◽

Bladder Tumor ◽

Interleukin 2 ◽

P53 Gene ◽

Clinical Effects ◽

Bacillus Calmette Guerin ◽

Bladder Tumors ◽

Cpg Oligodeoxynucleotides ◽

Cpg Oligodeoxynucleotide

Abstract Background CpG oligodeoxynucleotides, which boast anti-inflammatory, anti-infectious, and chemotherapeutic activities, are promising immunomodulators. Recently, some preclinical studies have highlighted the potent immunostimulatory and anti-tumor effects of CpG oligodeoxynucleotides, which has aroused interest in their potential clinical effects on human cancers. Methods In this study, we evaluated the therapeutic effect of a new type of CpG oligodeoxynucleotide whose sequence (5’-AACGTTGTCGTCGACGTCGTCGTCAGGCCTGACGTTATCGATGGCGTTGTCGTCAACGTTGTCGTTAACGTT-3’) was designed by our laboratory in combination with epirubicin in a bladder tumor rat model induced by N-methyl-N-nitrosourea instillation. Moreover, we explored the safety of the novel CpG oligodeoxynucleotide for bladder tumor therapy by observing the degree of cystolith in the bladder and comparing the results against those of Bacillus Calmette–Guérin therapy, which is a gold-standard treatment for bladder tumor. Results All results showed that CpG oligodeoxynucleotide combined with epirubicin significantly inhibited the growth of bladder tumors and reduced the pathological grading. As compared with bladder cells or cytokines observed under the positive control or epirubicin-alone treatment conditions, all indexes including histopathological grading, Mutation P53 gene protein expression, and Interleukin-2 (IL-2) level were significantly optimized by instillation of CpG oligodeoxynucleotide. Immunohistochemical examination indicated that CpG oligodeoxynucleotide reduced the expression of Mutation P53 gene protein in the bladder tumor rat model. Specifically, the level of IL-2 in rat serum was increased by more than 30% CpG oligodeoxynucleotide treatment combined with epirubicin. Also, in comparison with the degree of cystolith observed in the Bacillus Calmette–Guérin group, no obvious side effects were caused by CpG oligodeoxynucleotide. Conclusions CpG oligodeoxynucleotide as an immunomodulator can enhance the efficacy of epirubicin and presents higher safety than Bacillus Calmette–Guérin in treating bladder cancer.

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Investigation of the Effective Dose of Agonistic 4-1BB Monoclonal Antibody in a Murine Colon Cancer Metastasis Model

Journal of the Korean Surgical Society ◽

10.4174/jkss.2010.78.1.7 ◽

2010 ◽

Vol 78 (1) ◽

pp. 7

Author(s):

Jong Man Kim ◽

Sung Joo Kim ◽

Jae-Won Joh ◽

Choon Hyuck David Kwon ◽

Haejung Park ◽

...

Keyword(s):

Monoclonal Antibody ◽

Colon Cancer ◽

Effective Dose ◽

Cancer Metastasis ◽

Colon Cancer Metastasis ◽

Metastasis Model ◽

Murine Colon

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Therapeutic effect of recombinant interleukin-2 against chronic hepatitis type B.

Kanzo ◽

10.2957/kanzo.29.158 ◽

1988 ◽

Vol 29 (2) ◽

pp. 158-167

Author(s):

Hajime KONDO

Keyword(s):

Chronic Hepatitis ◽

Therapeutic Effect ◽

Interleukin 2 ◽

Type B ◽

Chronic Hepatitis Type ◽

Recombinant Interleukin 2 ◽

Hepatitis Type B

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Investigation of the Optimum Preparation of Peach Gum Polysaccharides and the In Vivo and In Vitro Therapeutic Effects on Acute Pyelonephritis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2729343 ◽

2019 ◽

Vol 2019 ◽

pp. 1-19

Author(s):

Feifei Zhang ◽

Jie Bai ◽

Yao Zheng ◽

Shuai Liang ◽

Lei Lei ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Therapeutic Effect ◽

Acute Pyelonephritis ◽

Interleukin 2 ◽

Urine Volume ◽

Therapeutic Effects ◽

Peach Gum

Background. Acute pyelonephritis (APN), known as stranguria in traditional Chinese medicine, is commonly treated with antibiotics. However, the rise in antibiotic resistance and the high rates of recurrence of APN make its treatment complicated, thus the development of alternative therapies is critical. Peach gum has long been recognized by traditional Chinese medicine as a food with medicinal value of relieving stranguria, but whether and how its primary constituent peach gum polysaccharides (PGPs) contribute to the diuretic function is still not clear. Purpose. The aim of this study was to investigate the optimum extraction process of PGPs and to evaluate its therapeutic effect on APN rats and to discover the underlying mechanism. Methods. In this study, surface design optimization was adopted to optimize the preparation of PGPs and HPLC and FT-IR spectra were used to evaluate the quality of PGPs; APN model rat was established by the Escherichia coli urinary tract infection method; the therapeutic effect and mechanism of PGPs on APN were determined by the visceral index, biochemical indicators, pathological section of the APN rat, and diuretic activity on mice and antibacterial activity in vitro. Results. Compared with an untreated APN group, the results showed that treatment with PGPs increased the APN-induced attenuation of secretory immunoglobulin A (sIgA) and creatinine clearance and decreased the APN-induced enhancement of the number of white blood cell (WBC), neutrophil counts (NC), bacteria load of the kidneys, kidney index, serum creatinine, urine volume, blood urea nitrogen (BUN), and interleukin-2 (IL-2) levels. The mechanism underlying these effects was further elucidated through in vitro experiments of the antibacterial and antiadhesion effects of PGPs. Conclusion. Due to the good therapeutic effects and advantages of PGPs, it could be considered as an alternative medicine to treat APN.

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