通过联合使用粒细胞集落刺激因子动员的干细胞或骨髓和/或脾脏细胞,加上化疗环磷酰胺疫苗接种,增强抗癌治疗和抗氧化应激的免疫功能。

IF 3.3 4区 医学 Q3 IMMUNOLOGY
Soha Gomaa, Mohamed Nassef, Ghada Tabl, Shaimaa El Gabry
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引用次数: 0

摘要

免疫治疗和化疗的结合,被称为化学免疫治疗,代表了一种有前途的方案,用于开发针对局部肿瘤微环境和早期肿瘤的新癌症治疗方法。然而,这种方法有潜在的风险,包括骨髓和免疫抑制,以及化疗耐药肿瘤细胞的出现。本研究的目的是研究动员造血干细胞(hsc)在与化疗和免疫治疗一起使用时如何增强和调节免疫反应,从而克服免疫抑制并消除远处癌细胞。采用CTX (4 mg/只)腹腔预处理Ehrlich禁欲癌(EAC)荷瘤小鼠。经CTX预处理的载瘤小鼠通过侧尾静脉静脉注射5 × 106的过继性转移小鼠源性骨髓细胞(nBMCs组),5 × 106细胞/只的过继性转移载瘤小鼠源性骨髓细胞(tBMCs组),5 × 106的过继性转移naïve小鼠源性骨髓细胞(nBMCs)和naïve小鼠源性脾细胞(nSPs)的组合(nBMCs/nSPs组)将过继转移的荷瘤小鼠来源的骨髓细胞(tBMCs)和荷瘤小鼠来源的脾细胞(tsp)按5 × 106个细胞/只(tBMCs/ tsp组),或5µg/只(g - csf组)皮下注射g - csf (s.c.)。随后,所有小鼠组均接种肿瘤裂解液,剂量为100µg/只。用G-CSF、过继转移nBMCs、过继转移tBMCs、过继转移nBMCs/nSPs、过继转移tBMCs/tSPs处理EAC荷瘤小鼠,其抗肿瘤作用显著增强,表现为对EAC肿瘤细胞的抗增殖活性和生长抑制增强,EAC肿瘤细胞坏死率和凋亡率增加,EAC荷瘤小鼠肿瘤生长受到限制。癌胚抗原(CEA)肿瘤标志物水平降低。此外,接受G-CSF、过继转移tBMCs、过继转移nBMCs/nSPs和过继转移tBMCs/ tsp治疗的EAC荷瘤小鼠血清中抗氧化酶超氧化物歧化酶(SOD)和丙二醛(MDA)水平均有改善。值得注意的是,这种治疗方案改善了与CTX给药有关的EA荷瘤小鼠的肝脏和肾脏损害。g - csf动员的造血干细胞、过继性转移的nBMCs、过继性转移的tBMCs、过继性转移的nBMCs/nSPs联合以及过继性转移的tBMCs/tSPs联合的整合可能产生强大的抗癌治疗,从而促进更有效的抗肿瘤免疫治疗策略,并与抗肿瘤反应相结合。本研究可能提出一种结合化疗和免疫治疗的治疗早期癌症的新方法。进一步的研究需要将该方案的生物医学应用和人类肿瘤和免疫系统的异质性与诊断和治疗方法联系起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immunoenhancing of the anti-cancer therapy and anti-oxidative stress by co-administration of granulocyte-colony stimulating factor-mobilized stem cells or cells derived from bone marrow and/or spleen plus vaccination with chemotherapeutic cyclophosphamide.

The combination of immunotherapy and chemotherapy, referred to as chemo-immunotherapy, represents a promising regimen for developing new cancer treatments that target the local tumor microenvironment and target tumors in their early stages. However, this approach carries potential risks, including myelo- and immunosuppression, as well as the emergence of chemo-resistant tumor cells. The purpose of this study was to investigate how well mobilizing hematopoietic stem cells (HSCs) work when used alongside chemotherapy and immunotherapy to enhance and modulate the immune response, thereby overcoming immunosuppression and eliminating distant cancer cells. Ehrlich ascetic carcinoma (EAC) tumor-bearing mice were intraperitoneal (i.p.) preconditioned with CTX (4 mg/mouse). EAC-bearing mice that were preconditioned with CTX were intravenous (i.v.) administered with adoptive transferred naive mice-derived bone marrow cells (nBMCs) at 5 × 106 through lateral tail vein (nBMCs group), adoptive transferred tumor-bearing mice-derived bone marrow cells (tBMCs) at 5 × 106 cell/mouse (tBMCs group), a combination of adoptive transferred naïve mice-derived bone marrow cells (nBMCs) and naïve mice-derived splenocytes (nSPs) at 5 × 106 (nBMCs/nSPs group), a combination of adoptive transferred tumor-bearing mice-derived bone marrow cells (tBMCs) and tumor-bearing mice derived-splenocytes (tSPs) at 5 × 106 cell/mouse (tBMCs/tSPs group), or G-CSF administrated subcutaneously (s.c.) at 5 µg/mouse (G-CSF group). Subsequently, all mice groups were vaccinated with tumor lysate at a dosage of 100 µg/mouse. Treating EAC tumor-bearing mice with G-CSF, adoptive transferred nBMCs, adoptive transferred tBMCs, adoptive transferred nBMCs/nSPs, adoptive transferred tBMCs/tSPs, resulted in a significantly enhanced anti-tumor effect that was evidenced by increased anti-proliferative activity and growth inhibition against EAC tumor cells, increased necrosis and apoptosis rates among EAC tumor cells, restricted tumor growth in EAC tumor-bearing mice, and reduced levels of carcinoembryonic antigen (CEA) tumor marker. Furthermore, there was an improvement in serum levels of antioxidant enzyme superoxide dismutase (SOD) and malondialdehyde (MDA) in EAC tumor-bearing mice receiving G-CSF, adoptive transferred tBMCs, adoptive transferred nBMCs/nSPs, and adoptive transferred tBMCs/tSPs. Notably, this treatment regimen ameliorates liver and kidney damage associated with CTX administration in EA tumor-bearing mice. The integration of G-CSF-mobilized HSCs, adoptive transferred nBMCs, adoptive transferred tBMCs, adoptive transferred nBMCs/nSPs combination, and adoptive transferred tBMCs/tSPs combination may yield powerful anti-cancer therapy, thereby facilitating more effective anti-tumor immunotherapy strategies when align with anti-tumor responses. This research may propose a novel therapeutic approach that combines chemotherapy and immunotherapy for addressing early-stage cancer. Further research is necessary to connect the biomedical application and heterogeneity of human tumors and immune systems of this regimen to both diagnostic and therapeutic methodologies.

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来源期刊
Immunologic Research
Immunologic Research 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
83
审稿时长
6-12 weeks
期刊介绍: IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.
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