The development of tailings in concrete technology is not only conducive to the realization of the goal of reducing carbon emissions, but also conducive to the inhibition the occurrence of shortages of sand and gravel supplies. In this study, graphite tailings were used to replace sand in the range of 0~100%, and the mechanical mechanism of graphite tailings concrete was examined through compressive and flexural tests. The mechanical experimental results were evaluated and verified based on concrete macroscopic failure appearance, mesoscopic failure appearance, and physical characteristics of graphite tailings. The results revealed that the concrete strength increases first and then decreases with the increase of the graphite tailings content. Compared to GT00 (GT00 is a specimen with a graphite tailings content of 0%, and so on), GT10~GT60 exhibited better mechanical properties, of which 30% was recommended as the optimal replacement rate. The mechanical properties of GT10 and GT20 had an upward trend, and GT30 had low spalling, with aggregate fragmentation found on the fracture surface. GT30 showed the best resistance to bending and deformation. The mechanical properties of GT40~GT60 had a downward trend. When the graphite tailings content was higher than 70%, the interface defects of the aggregate matrix increased, thus making it easier for cracks to propagate along the interface. Furthermore, the mechanism of graphite tailings replacing sand verified the test results from different perspectives, which provides new analysis ideas for other tailings in environment-friendly concrete.

项与 GT-30 (x) 相关的新闻（医药）

2024-04-11

·Firstwordpharma

AACR24: Cancer vaccines find foothold in immunotherapy combos, relapse prevention

After falling out of favour following a series of clinical failures, cancer vaccines may have finally found their niches in the cancer treatment paradigm. Data presented at this year’s American Association for Cancer Research (AACR) annual meeting suggest cancer vaccines might be effective in treating later-stage patients in combination with established immunotherapies, and to prevent relapse.Moderna notches second winAfter demonstrating the potential of its personalised cancer vaccine to treat melanoma at last year’s American Society of Clinical Oncology (ASCO) meeting, Moderna shared Phase I data from a different tumour type at AACR, suggesting its versatility.Moderna is partnered with Merck & Co. to develop mRNA-4157 (V940), an mRNA-based individualised neoantigen therapy that encodes up to 34 neoantigens inducing specific anti-tumour T-cell activation. In 22 patients with unresectable, metastatic HPV-negative head and neck squamous cell cancer (HNSCC), mRNA-4157 plus Merck's anti-PD-1 antibody Keytruda (pembrolizumab) led to a response rate of 27.3%.The data was sufficient to add about 6% to Moderna’s market cap, one of the biggest gains seen by a biotech on the back of conference data. For more market analysis, see Vital Signs: AACR24’s most impactful market movers.Keytruda combo success for GeneosGeneos Therapeutics shared Phase I/II data of GT-30, a DNA plasmid encoded personalised therapeutic cancer vaccine (PTCV) that may include up to 40 neoantigens, as a second-line treatment for hepatocellular carcinoma patients who have previously received a multi-tyrosine kinase inhibitor.In combination with DNA plasmid encoded IL-12 and Keytruda, the PTCV led to an observed response rate (ORR) of 30.6% in 36 evaluable patients, including three complete responses (CRs). Based on a 16.9% ORR historical benchmark for Keytruda monotherapy, GT-30 achieved a statistically significant response rate. At the data cutoff, patients who received GT-30 had a median overall survival (OS) of 19.9 months compared with a historical OS range of 12.9 – 15.1 months for Keytruda. "Other recent industry trials have tested personalised cancer vaccines in patients with highly immune-sensitive tumour phenotypes and no measurable disease. In marked contrast, the GT-30 trial assesses PTCVs in HCC, a cancer with very low tumour mutational burden and an immune-excluded phenotype, and in patients with significant late-stage unresectable and metastatic disease," said Geneos CEO Niranjan Sardesai. “We have not only met endpoints for safety, immunogenicity, and clinical efficacy based on ORR in this difficult-to-treat setting, but our mechanism of action data trace and confirm every step, from vaccination to tumour reduction, required to explain the immunological basis for the observed clinical responses."Long-term data for Genentech, BioNTech Vinod Balachandran, a surgical oncologist and researcher at the Memorial Sloan Kettering Cancer Center (MSKCC), presented three-year follow-up data from an MSKCC-sponsored Phase I trial of autogene cevumeran – an individualised mRNA vaccine from partners Genentech and BioNTech that targets up to 20 unique neoantigens identified from each patient’s tumour.Of the 16 evaluable patients with resectable pancreatic cancer who received autogene cevumeran in combination with Roche’s PD-L1 inhibitor Tecentriq (atezolizumab) and modified FOLFIRINOX chemotherapy, half experienced induced immune responses, as measured by high-magnitude neoantigen-specific T-cell expansion. After a median follow-up of three years, those eight patients with vaccine-induced T-cell responses had still not reached median recurrence-free survival, compared with 13.4 months for the eight patients whose immune systems did not respond to the cancer vaccine.“The findings that individualised neoantigen-specific cancer vaccines can induce a robust immune response that correlates with delayed disease recurrence continues to support these vaccines as an encouraging therapeutic approach for pancreatic cancer,” Balachandran said.Transgene seeks to delay relapse Transgene developed TG4050, a personalised cancer vaccine that uses a nonpathogenic form of poxvirus to deliver 30 neoantigens, to delay relapse of surgically resected tumours. In a Phase I trial of 33 patients with stage 3 or 4 surgically resected HPV-negative HNSCC who have also undergone standard-of-care radiation and chemotherapy, TG4050 induced tumour-specific immune responses and led to low rates of disease relapse. Of the 17 patients who received the cancer vaccine immediately after standard of care, none relapsed after a median follow-up of 16.2 months. In the 16-patient observational arm, three experienced disease relapse: one after 6.2 months, another after 8.8 months, and a third after 18.5 months. Participants in the cohort are eligible to receive TG4050 following relapse. All but one of the vaccinated patients showed evidence of activated neoantigen-specific T cells in response to TG4050, which was individualised for each patient using AI and machine learning tools to analyse their tumour’s genome and identify relevant mutations and immunogenic neoantigens.“A therapeutic vaccine tailored to each patient’s unique tumour may lead to strong immune responses, which could eliminate any minimal residual disease that may eventually lead to disease relapse,” said Olivier Lantz, a clinical immunologist and researcher at Institut Curie in Paris.

疫苗临床结果临床1期AACR会议免疫疗法

2024-04-07

·PRNewswire

Geneos Therapeutics Announces Positive Phase 1/2 Data for GT-30 Trial of Personalized Therapeutic Cancer Vaccine

Trial has met primary endpoints of safety and immunogenicity and secondary endpoint for efficacy based on response rate Trial data published today in Nature Medicine Selected clinical trial data also presented at the 2024 AACR Annual Meeting PHILADELPHIA, April 7, 2024 /PRNewswire/ -- Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCVs), today announced the publication of positive safety, immunogenicity, and efficacy data from the full cohort of patients enrolled in its GT-30 clinical trial in Nature Medicine. The paper, titled, "Personalized Neoantigen Vaccine and Pembrolizumab in Advanced Hepatocellular Carcinoma: A phase 1/2 trial," details the GT-30 clinical trial, a 36-patient, single-arm, open-label, multi-center Phase 1/2 study of GNOS-PV02, a DNA plasmid encoded PTCV in combination with DNA plasmid encoded IL-12 (a cytokine adjuvant), and pembrolizumab (a PD-1 inhibitor) in second-line (2L) patients with advanced hepatocellular carcinoma (HCC) previously treated with a multi-tyrosine kinase inhibitor. The study met its primary endpoints of safety and immunogenicity and its secondary endpoint of efficacy based on observed response rate (ORR). PTCV-related adverse events were all limited to Grades 1 and 2 with no dose-limiting toxicities or grade > 3 adverse events observed. The most common adverse events were injection site reactions observed in 41.6% (15/36) of patients. This is in contrast to typical immuno-oncology combination regimens, including those approved for first-line use in advanced HCC, wherein adding a second agent may lead to markedly increased toxicity; here, the addition of a PTCV to a PD-1 inhibitor was not observed to lead to any significant decrease in patient safety and tolerability. The ORR for GT-30 is currently at 30.6% (11/36), including three complete responses (CR) and eight partial responses. This response is statistically significant based on pre-specified criteria at a one-sided p-value = 0.031 (1-sided 90% CI 20.4%-100%) versus a pre-specified historical control of 16.9% for pembrolizumab monotherapy. This historical comparator response rate was modeled on Phase 3 KN-240 data presented at ASCO 2019 and is also consistent with the prior Phase 2 KN-224 study. As an overall class, anti-PD1 monotherapy for 2L advanced HCC has shown response rates of 11%-18% in seven Phase 2 and Phase 3 clinical studies enrolling over 1400 patients. Additionally, the GT-30 CR rate of 8.3% (3/36) compares with a historical anti-PD-1 monotherapy CR rate in 2L of 0% - 3% in the prior studies. As of the data cutoff, the median OS (mOS) in GT-30 was 19.9 months compared to a mOS range of 12.9 – 15.1 months reported for the prior 2L studies of pembrolizumab and other anti-PD-1 monotherapy. 11 of 36 patients remain on treatment and, in total, 17 patients continue to be followed for overall survival (OS). "Other recent industry trials have tested personalized cancer vaccines in patients with highly immune-sensitive tumor phenotypes and no measurable disease. In marked contrast, the GT-30 trial assesses PTCVs in HCC, a cancer with very low tumor mutational burden and an immune-excluded phenotype, and in patients with significant late-stage unresectable and metastatic disease," said Niranjan Sardesai, PhD, CEO and president of Geneos. "Despite the small size of this study, our results are important for the advancement of the field. We have not only met endpoints for safety, immunogenicity, and clinical efficacy based on ORR in this difficult to treat setting, but our mechanism of action data trace and confirm every step, from vaccination to tumor reduction, required to explain the immunological basis for the observed clinical responses." Immunological analyses confirm the induction of new T cell responses to vaccine-encoded neoantigens in 14 of 14 (100%) evaluated patients and the expansion of this TCR repertoire both in the peripheral blood and tumors of PTCV-treated patients. Single cell sequencing analyses show the vast majority of these T cell clones to be CD8 T effector memory cells, a key requirement to induce anti-tumor cytotoxicity. In contrast, while anti-PD-1 monotherapy has been observed to reverse T cell dysfunction in existing neoantigen-specific T cell clones, it is not known to induce any new neoantigen-specific T cell clones. Today Geneos also presented selected GT-30 clinical trial data and updated longitudinal circulating tumor DNA (ctDNA) biomarker data from the trial at the 2024 American Association for Cancer Research (AACR) Annual Meeting in San Diego. Reductions of at least 50% versus baseline in patient ctDNA, an exploratory endpoint, were seen in 40.7% of patients (11 of 27 patients for whom the full data set are available). All such responses correlate with ongoing survival. "To our knowledge, the GT-30 clinical study provides the first definitive demonstration of a personalized cancer vaccine enhancing clinical response to anti-PD-1 therapy by inducing new, neoantigen-specific T cells which traffic to the tumor," said Ildiko Csiki, MD, PhD, chief medical officer of Geneos. "The fact that the PTCV regimen has produced this important result in a form of cancer as immunologically 'cold' as HCC, leading to multiple complete responses and a doubling of objective response versus PD-1, is incredibly promising and shows the therapeutic potential of personalized cancer vaccines for cancer patients." DNA-based PTCVs may include up to 40 neoantigens. The majority of patients in the GT-30 study were administered PTCVs which included all of their targetable neoantigens across a broad range of predicted MHC binding affinity. A correlation was seen in GT-30 between the number of vaccine epitopes and the number of reactive epitopes post-vaccination, suggesting that having more neoantigens in the vaccine increased the effectiveness of tumor control. Other personalized vaccine platforms, especially those not based on DNA, have historically had to target a more limited selection of neoantigens, which may limit their efficacy. About Geneos Therapeutics Geneos Therapeutics, a clinical stage biotherapeutics company, is developing personalized therapeutic cancer vaccines (PTCVs) that may serve an important role in new immunotherapeutic paradigms for cancer. The company's approach, using its proprietary GT-EPIC™ platform, is to target neoantigens (abnormal mutations produced by cancer cells) from individual patient tumors to develop novel and uniquely personalized treatments for cancer. Planning is underway for a potentially registrational clinical trial in advanced hepatocellular carcinoma. For more information, please visit . This press release contains certain forward-looking statements relating to our business, including our plans regarding the development of personalized therapeutic cancer vaccines and the therapeutic potential and clinical benefits of our product candidates. Actual events or results may differ from the expectations set forth herein. There can be no assurance that any product candidate in Geneos' pipeline will be successfully developed, manufactured or commercialized, that final results of clinical trials will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and Geneos undertakes no obligation to update or revise these statements, except as may be required by law. This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities. SOURCE Geneos Therapeutics, Inc.

临床结果疫苗AACR会议免疫疗法临床2期

100 项与 GT-30 (x) 相关的药物交易

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