Department of Medicine, Case Western Reserve University, Cleveland, OH, United States.
Medical Affairs, Partner Therapeutics, Inc., Lexington, MA, United States.
Front Immunol. 2021 Aug 17;12:706186. doi: 10.3389/fimmu.2021.706186. eCollection 2021.
BACKGROUND: Sargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery in diverse settings of bone marrow failure and is designated on the list of FDA Essential Medicines, Medical Countermeasures, and Critical Inputs. Other important biological activities including accelerating tissue repair and modulating host immunity to infection and cancer the innate and adaptive immune systems are reported in pre-clinical models but incompletely studied in humans. OBJECTIVE: Assess safety and efficacy of sargramostim in cancer and other diverse experimental and clinical settings. METHODS AND RESULTS: We systematically reviewed PubMed, Cochrane and TRIP databases for clinical data on sargramostim in cancer. In a variety of settings, sargramostim after exposure to bone marrow-suppressing agents accelerated hematologic recovery resulting in fewer infections, less therapy-related toxicity and sometimes improved survival. As an immune modulator, sargramostim also enhanced anti-cancer responses in solid cancers when combined with conventional therapies, for example with immune checkpoint inhibitors and monoclonal antibodies. CONCLUSIONS: Sargramostim accelerates hematologic recovery in diverse clinical settings and enhances anti-cancer responses with a favorable safety profile. Uses other than in hematologic recovery are less-well studied; more data are needed on immune-enhancing benefits. We envision significantly expanded use of sargramostim in varied immune settings. Sargramostim has the potential to reverse the immune suppression associated with sepsis, trauma, acute respiratory distress syndrome (ARDS) and COVID-19. Further, sargramostim therapy has been promising in the adjuvant setting with vaccines and for anti-microbial-resistant infections and treating autoimmune pulmonary alveolar proteinosis and gastrointestinal, peripheral arterial and neuro-inflammatory diseases. It also may be useful as an adjuvant in anti-cancer immunotherapy.
背景：沙格司亭[重组人粒细胞-巨噬细胞集落刺激因子（rhu GM-CSF）]于 1991 年获得美国 FDA 批准，用于加速骨髓衰竭多种情况下的骨髓恢复，被列入 FDA 基本药物、医疗对策和关键投入清单。其他重要的生物学活性，包括加速组织修复和调节宿主对感染和癌症的免疫——先天和适应性免疫系统在临床前模型中已有报道，但在人类中研究尚不完整。
目的：评估沙格司亭在癌症和其他不同实验和临床环境中的安全性和疗效。
方法和结果：我们系统地检索了 PubMed、Cochrane 和 TRIP 数据库，以获取沙格司亭在癌症中的临床数据。在各种情况下，沙格司亭在暴露于骨髓抑制药物后加速了血液学恢复，导致感染减少、治疗相关毒性减少，有时还提高了生存率。作为一种免疫调节剂，沙格司亭还增强了实体瘤中的抗肿瘤反应，与常规疗法联合使用，例如与免疫检查点抑制剂和单克隆抗体联合使用。
结论：沙格司亭在多种临床环境中加速血液学恢复，并增强抗肿瘤反应，具有良好的安全性。除了在血液学恢复方面的应用外，其用途研究较少；需要更多关于免疫增强益处的数据。我们设想沙格司亭在不同的免疫环境中得到更广泛的应用。沙格司亭有可能逆转与脓毒症、创伤、急性呼吸窘迫综合征（ARDS）和 COVID-19 相关的免疫抑制。此外，沙格司亭治疗在疫苗辅助治疗、抗微生物耐药感染、治疗自身免疫性肺泡蛋白沉积症和胃肠道、外周动脉和神经炎症性疾病方面也很有前景。它也可能作为抗肿瘤免疫治疗的辅助药物。
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