Effect of expressing of anti-PD-1 antibody in mouse mammary gland on spleen T cells in transgenic mice / 生物工程学报

This study aims to investigate the effect of anti-PD-1 antibody expressed in mouse mammary gland on the surface antigen protein of spleen T cells, cytokine expression, spleen CD4+ T cell proliferation and proliferation related pathways of transgenic mice at the cellular level. Transgenic mice expressing anti-human PD-1 antibody at 8 weeks of age without pregnancy and 18 weeks of age with lactation were divided into two groups, with transgenic negative mice in each group as the control. Spleen lymphocytes were extracted and the changes of spleen lymphocytes were detected. Compared with transgenic negative mice, the proportion of effector T cells of spleen T cells in the immune system of transgenic mice with anti-PD-1 antibody expressed in breast increased, the proportion of Treg cells decreased, and the IFN-γ, IL-17 and IL-2 expressed in CD4+ T cells increased in varying degrees. Moreover, IL-4, IL-10 and TGF-β in CD4+ T cells did not change, nor did some cell surface protein molecules related to T cell stimulate. There was no significant difference in T cell proliferation between transgenic positive and transgenic negative mice. In transgenic positive mice, the expression of phosphorylated proteins in PI3K/Akt/mTOR and RAS/MEK/ERK pathways were partially up-regulated, but the whole pathway was not completely up-regulated. Therefore, it is feasible to use transgenic mice as host to express monoclonal antibodies related to immune system such as anti-PD-1 antibody.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Efficacy and safety of radiotherapy combined with targeted therapy, immunotherapy and chemotherapy for unresectable intrahepatic cholangiocarcinoma / 中华放射医学与防护杂志

Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.

Study on protective effect of Shenqi Fuzheng injection on immune myocarditis injury induced by anti-PD-1 antibody / 中国药理学通报

Aim To investigate the effeot of Shenqi Fuzheng injection on the prevention of immune myocarditis induced by anti-PD-1 antibody by reducing the production of inflammatory factors and the expression of myocardial injury markers. Methods Thirty-two maie PD-1 humanized mice with C57BL/6 genetic background were randomly divided into control group, myocarditis model group, anti-PD-1 antibody group and Shenqi Fuzheng injection group (n = 8). Except the control group, mice in other groups were intraperitoneally injected with myocardial myosin heavy chain peptide (5 mg • kg

A Real-world Study of Anti-PD-1 Antibody Combination Therapy in Advanced Hepatocellular Carcinoma / 肿瘤防治研究

Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Camrelizumab combined with microwave ablation improves the objective response rate in advanced non-small cell lung cancer

Aim: The present study evaluated the safety and efficacy of camrelizumab (a programmed death-1 antibody) in combination with microwave ablation (MWA) in advanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 21 patients were prospectively enrolled. MWA was performed in 25 pulmonary lesions during 21 sessions. Camrelizumab was administered 5–7 days after MWA as a dose of 200 mg, which was repeated every 2 weeks until disease progression or intolerable toxicities. The primary endpoints were safety and the objective response rate (ORR). Other endpoints included progression-free survival (PFS) and overall survival (OS). Results: The technical success rate was 100%. No treatment-associated deaths were identified. Major complications, minor complications, and side effects of MWA were observed in 9, 8, and 14 patients, respectively. The main major complications included pneumothorax, pneumonia, hemorrhage, and pleural effusion. The adverse events of camrelizumab included reactive skin capillary hyperplasia (n = 9), hypothyroidism (n = 5), pneumonia (n = 4), fatigue (n = 2), leukopenia (n = 1), and neutropenia (n = 1). Grade 2 and 3 camrelizumab adverse events were identified in eight and three patients, respectively. The ORR was 33.3%, with two patients achieving complete response and five patients achieving partial response. The median PFS was 5.1 months and OS was not reached. Conclusions: Camrelizumab administration combined with MWA was safe in the treatment of advanced NSCLC, and the combination improved the ORR of camrelizumab alone compared to previous reports

Collaborative study to evaluate a reporter gene assay for anti-PD-1 antibody bioactivity / 药学学报

A collaborative inter-laboratory validation was carried out using a reporter gene assay to measure the bioactivity of anti-PD-1 monoclonal antibody, in order to study the applicability and transferability of the method. In this study, two collaborative schemes were designed to measure the precision, linearity and accuracy of the method. The results showed that the 95% confidence interval (CI) of the intra-assay precision was (1.72-16.89) %, inter-assay precision was (2.63-17.67) %, inter-laboratory precision was (9.00-14.26) %, all linear correlation coefficients were greater than 0.99, and the 95% CI for the accuracy at different potency levels was (91.83-104.40) % at 50%, (90.40-101.40) % at 75%, (94.71-105.60) % at 100%, (94.00-102.00) % at 125%, and (96.73-104.30) % at 150%. The collaborative validation results proved that the reporter gene assay for the bioactivity determination of anti-PD-1 monoclonal antibody has good precision, linearity and accuracy, and could be applied to the release and stability analysis of anti-PD-1 monoclonal antibodies in different laboratories.

Lichen Planus Developed During the Treatment with Nivolumab in a Patient with Lung Cancer: A Case Report and Literature Review / 대한피부과학회지

Nivolumab is a fully-humanized IgG4 monoclonal antibody that competitively binds to the programmed cell death receptor-1 protein (an immune check-point molecule) present on activated T cells. Nivolumab is approved for the treatment of advanced melanoma, lung cancer, and renal cell carcinoma. It attenuates the inactivation of cytotoxic CD8+ T cells and, produces an antitumor effect; however it may be associated with immune-related adverse events, including the development of lichen planus (LP). A 72-year-old man presented with a 2-month history of multiple, polygonal, purplish papules on the dorsal aspect of both hands. He was diagnosed with large cell neuroendocrine carcinoma (LCNEC) of the lung 4 years earlier and was treated with nivolumab (3 mg/kg every 2 weeks) for 9 months. By the 14th course of nivolumab therapy, the patient developed multiple rashes on the dorsal aspect of both hands, and biopsy was consistent with findings of LP. We report a rare case of LP in a patient with lung cancer treated with nivolumab.

Advances of toripalimab for the treatment of melanoma / 中国肿瘤临床

On December 27, 2018, the first domestic anti-PD-1 antibody, toripalimab, was approved by the State Food and Drug Ad-ministration for the treatment of advanced melanoma after the failure of standard treatment. This represented a major breakthrough in the field of biopharmaceuticals in China and laid the foundations for pharmaceutical research and development in the field of tu-mor immunotherapy. In this article, we summarize the clinical research of the treatment of melanoma, the application of toripalimab in this field, and the global development of other anti-PD-1 antibodies, to provide guidance for the research and treatment of melano-ma in China.

The clinical reports on adrenal insufficiency of patients with advanced solid tumors accepting anti-PD-1 antibody, SHR-1210 therapy / 中华肿瘤杂志

Objective@#To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy.@*Methods@#The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency.@*Results@#Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210.@*Conclusions@#The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.

Blocking the PD-1/PD-L1 axis enhanced cisplatin chemotherapy in osteosarcoma in vitro and in vivo

BACKGROUND@#The blocking of the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis has been found to have an anticancer activity against various types of cancer by enhancing T cell immunity, while there are no studies linking the PD-1/PD-L1 axis to chemotherapy drugs in osteosarcoma (OS). The present study aimed to investigate the effects of blocking PD-1/PD-L1 axis on the cisplatin chemotherapy in OS in vitro and in vivo.@*METHODS@#Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to detect PD-L1 mRNA in OS tissues. Cell proliferation and apoptosis were measured by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. In vivo, the syngeneic mice were treated with cisplatin and anti-PD-1 antibody alone or jointly.@*RESULTS@#In this study, it revealed that PD-L1 mRNA was highly expressed in OS tissues. Further inhibitory evaluation showed that the K7M2-LV cells (PD-L1 overexpression) co-cultured with PD-1 lymphocytes could promote K7M2 cell proliferation. Meanwhile, the combination of anti-PD-1 antibody and cisplatin significantly decreased the proliferation and increased the apoptosis of K7M2 cells in a co-culture system. In vivo, the combination of anti-PD-1 antibody and cisplatin significantly inhibited tumor growth, while the mechanisms did not involve regulatory T cells.@*CONCLUSION@#The present data suggested that the blocking of PD-1/PD-L1 axis had a positive prognostic value, which can enhance the chemotherapeutic effect of cisplatin in OS. These findings provide a rationale for utilizing PD1/PD-L1 blocking antibodies as a single agent to cure refractory OS in patients receiving cisplatin treatment.

Clinical observation of thyroid-related adverse events induced by anti-PD-1 antibody SHR-1210 in patients with advanced solid tumor / 中华肿瘤杂志

Objective@#To assess the incidence and characteristics of thyroid dysfunction during anti-Programmed cell death 1 receptor (PD-1) antibody SHR-1210 therapy in patients with advanced solid tumor.@*Methods@#The medical records of 98 patients who initiated SHR-1210 treatment between April 27, 2016 and June 8, 2017 in the phase 1 trial to evaluate the safety, efficacy, and pharmacokinetics of SHR-1210 in patients with advanced solid tumors were retrospectively reviewed. Serological tests of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at baseline and prior to each SHR-1210 administration.@*Results@#A total of 86 patients had normal thyroid function before the first dose of SHR-1210 treatment. Nine out of 86 (10.5%) patients developed new onset hypothyroidism from euthyroid state. 12 patients presented thyroid dysfunction at baseline, 10 of whom were subclinical hypothyroid and 2 were hypothyroidism. Four out of 10 patients developed hypothyroidism from subclinical hypothyroid. Most patients with hypothyroidism were asymptomatic. Thyroid dysfunction occurred early (median, 55days) after the initiation of SHR-1210. The severity of hypothyroidism were all grade 1-2. No grade 3-4 hypothyroidism occurred. No patients discontinue the treatment of SHR-1210 due to clinical impact of the thyroid dysfunctions.@*Conclusions@#Thyroid-related adverse events were common during anti-PD-1 antibody SHR-1210 treatment . The incidence of hypothyroidism is lower in patients with euthyroid state than in patients with thyroid dysfunction at baseline during SHR-1210 treatment . Thyroid function can be improved after thyroid hormone replacement. During SHR-1210 treatment, it is necessary to pay attention to monitor the thyroid function, especially in the patients with thyroid dysfunction at baseline.@*Trial registration@#Chinese Clinical Trial Registry, 2016L01455

PD-1 antibody enhanced anti-tumor efficacy of oxaliplatin against colon cancer in vitro and in vivo / 中国肿瘤生物治疗杂志

@#Objective: To explore the anti-tumor effects of oxaliplatin (OXA) combined with PD-1 antibody on colon cancer. Methods: Flow cytometry was used to detect the expression of PD-L1 in colon cancer cell lines HCT-116 and HT-29. Co-culture method was used to detect the secretion of cytokines and the changes of CD4/CD8 subsets in T-cells that co-cultured with HCT-116 cells, which were pretreated with OXAin combination with/without PD-1 antibody; The CT26 transplanted tumor model of colon cancer in BALB/c mice was established and treated with the combination of OXA and PD-1 to evaluate their anti-tumor efficacy. Meanwhile, CD8 antibody was used to scavenge CD8+ T cells in mice, and to evaluate the role of CD8+ T cells in the anti-tumor effect of OXA in vivo. Results: OXAcould significantly increase the expression of PD-L1 on the surface of colon cancer cells. Compared with pure T-cells, the T cells co-cultured with colon cancer HCT-116 cells that pre-treated by OXA, exhibited significantly reduced IL-2, IFN-γ and TNF levels (all P<0.05) in its culture supernatant and decreased ratio of CD4+memory T cell / CD8+TEMER (P<0.05), whereas there was increased cell proportion of the CD4+ (P>0.05) and CD8+ (P<0.05) naïve T cells. After co-treated with PD-1 antibody, compared with the single treatment of OXA, IFN-γ and IL-10 content (P<0.05) in culture supernatant and the subsets of CD8+ TCM and TEMRA ratio (P>0.05) were increased. In vivo experiments showed that OXAcombined with PD-1 antibody could enhance its anti-tumor activity, the tumor suppression rates were 25.6% (OXA) and 29.1% (αPD-1), respectively, however, the rate of tumor inhibition was increased to 58.2% when combined (P<0.05, compared to OXA or αPD-1 group). After scavenging CD8+T cells in mice, the antitumor activity of OXA dropped from 68.4% to 46.2% (P<0.05). Conclusion: OXA combined with PD-1 antibody had synergistic anti-tumor effect, and CD8+ T cells played an important role in the antitumor activity of OXA.

Research progress on the mechanism and clinical data of IDO inhibitor in reversing the resistance of malignancies to PD-1 antibody by regulating MDSCs / 中国肿瘤临床

PD-1 antibody immunotherapy has been used as a first-line treatment against various malignancies,but resistance to this treatment limits its efficacy.For instance,myeloid derived suppressor cells,myeloid derived suppressor cells induce resistance to PD-1 antibody in a tumor microenvironment.A few combination regimens of an IDO inhibitor plus PD-1 antibody are currently subjected to ongoing clinical trials in the US,and preliminary results have shown that this inhibitor can reverse the resistance of malignancies to PD-1 antibody.This study reviewed the research progress on the resistance mechanism of malignancies to PD-1 antibody and revealed that IDO inhibitor regulates MDSCs to reverse the resistance to PD-1 antibody.This study also described the clinical efficacy of this in-hibitor plus PD-1 antibody.

Advances in molecular targeted therapy for soft tissue sarcomas / 中国肿瘤临床

Sarcomas are tumors of mesenchymal origin that account for approximately 1%of human cancers. There are at least 60 dif-ferent subtypes of soft tissue sarcoma (STS). However, most tumor types are highly malignant tumors that lack an optimal therapeutic agent. Although gastrointestinal stromal tumor (GIST) responds well to imatinib, other types of STSs remain challenging because of their heterogeneous genetic and clinical features and poor prognosis. In recent years, the field of molecular targeted therapy has pro-gressed rapidly. Patients with advanced disease can receive individualized treatment to improve their quality of life. This review focus-es on the targeted therapies that have been evaluated for advanced non-GIST STS. Other promising novel therapeutic agents that are currently in the early phases of investigation are also presented.

Research progress on the mechanism and clinical data of IDO inhibitor in reversing the resistance of malignancies to PD-1 antibody by regulating MDSCs / 中国肿瘤临床

PD-1 antibody immunotherapy has been used as a first-line treatment against various malignancies,but resistance to this treatment limits its efficacy.For instance,myeloid derived suppressor cells,myeloid derived suppressor cells induce resistance to PD-1 antibody in a tumor microenvironment.A few combination regimens of an IDO inhibitor plus PD-1 antibody are currently subjected to ongoing clinical trials in the US,and preliminary results have shown that this inhibitor can reverse the resistance of malignancies to PD-1 antibody.This study reviewed the research progress on the resistance mechanism of malignancies to PD-1 antibody and revealed that IDO inhibitor regulates MDSCs to reverse the resistance to PD-1 antibody.This study also described the clinical efficacy of this in-hibitor plus PD-1 antibody.

Clinical observation and literature review of PD-1 antibody in the treatment of 18 patients with advanced tumor / 药学实践杂志

Objective To observe the immune effect of PD-1 (programmed death-1) antibody in the treatment of patients with advanced cancer .Methods From October 2015 to March 2016 ,18 patients with advanced tumor were selected to receive the PD-1 antibody treatment in Eastern Hepatobiliary Surgical Hospital .Clinical efficacy ,adverse reactions and progression free survival time were monitored .The quality of life were compared before and after the treatment .Results Among 18 cases , PR 5 cases ,SD 7 cases and PD 6 cases .The KPS scores for quality of life was significantly increased (P<0 .05) after treat-ment .At the end of follow-up ,5 patients died ,2 patients were lost in follow-up ,11 patients survived .The median progression free survival was 2 .6 months (95% CI:1 .8-3 .3 months) .No serious adverse reactions and abnormal laboratory results were reported .Conclusion PD-1 antibody is a safe and effective treatment for advanced tumors .It is well tolerated and has less ad-verse reactions .The randomized control studies with larger samples are needed to further confirm our conclusions .

Blockage of PD-L1/PD-1 pathway for enhancing the chemotherapeutic efficacy of cisplatin / 实用医学杂志

Objective To explore the anti-tumor effect and the influence of antitumor immunity of PD-L1/PD-1 blocked by PD-1 antibody combined with cisplatin. Methods Tumor models were established by injecting TC-1 cells into C57BL/6 mice, and the mice were divided into four groups (n = 4). The tumor growth curves and survival curves were drawn to observe the anti-tumor effect. The tumors were then removed; and the PD-L1 and CD8+ T cells were analyzed by immunohistochemical method. Results The anti-tumor effect was greater in the cisplatin group , PD-1 antibody group , and PD-1 antibody plus cisplatin group than in the control group (P < 0.05). Expression of PD-L1 in the tumor tissues was markedly increased in the cisplatin group and it was obviously decreased in the combination group (P < 0.05). CD8+ T cells decreased in the cisplatin group; and expression of CD8+ T cells was significantly increased the combination group (P < 0.05). Conclusion The anti-tumor effect and anti-tumor immunity of cisplatin are enhanced by blocking PD-L1/PD-1 pathway with PD-1 antibody.

Advance development of immunotherapy on malignant melanoma with targeting inhibition of PD-L1/ PD-1 / 中国药学杂志

Malignant melanoma presents a significant therapeutic challenge to clinicians with characteristics of early metastasis, rapid development, poor prognosis and high mortality. Many therapies for metastatic melanoma are limited by these characteristics. With the development of immunotherapy mechanism for malignant melanoma, a large number of antibody agents for the treatment of malignant melanoma entered the clinical trials. To our great delight, the new drugs of pembrolizumab and nivolumab have been approved by FDA in 2014 after successfully passing phase III clinical trial, which bring a chance of survival to patients with unresectable or metastatic advance melanoma. This review briefly discusses recent development and advances of anti-PD-L1/PD-1 antibody drugs against melanoma.