Pancreatic cancer kills millions of people worldwide each year and is one of the most prevalent causes of mortality that requires prompt therapy. A large number of people suffering from pancreatic cancer are detected at an advanced stage, with incurable and drug-resistant tumor, hence the overall survival rate of pancreatic cancer is less. The advance phase of this cancer is generated because of expression of the cancer-causing gene, inactivation of the tumorsuppressing gene, and deregulation of molecules in different cellular signalling pathways. The prompt diagnosis through the biomarkers significantly evades the progress and accelerates the survival rates. The overexpression of Mesothelin, Urokinase plasminogen activator, IGFR, Epidermal growth factor receptor, Plectin-1, Mucin-1 and Zinc transporter 4 were recognized in the diagnosis of pancreatic cancer. Nanotechnology has led to the development of nanocarriersbased formulations (lipid, polymer, inorganic, carbon based and advanced nanocarriers) which overcome the hurdles of conventional therapy, chemotherapy and radiotherapy which causes toxicity to adjacent healthy tissues. The biocompatibility, toxicity and large-scale manufacturing are the hurdles associated with the nanocarriers-based approaches. Currently, Immunotherapybased techniques emerged as an efficient therapeutic alternative for the prevention of cancer. Immunological checkpoint targeting techniques have demonstrated significant efficacy in human cancers. Recent advancements in checkpoint inhibitors, adoptive T cell therapies, and cancer vaccines have shown potential in overcoming the immune evasion mechanisms of pancreatic cancer cells. Combining these immunotherapeutic approaches with nanocarriers holds great promise in enhancing the antitumor response and improving patient survival.

2025-02-01·Combinatorial Chemistry & High Throughput Screening

Current Perspectives of Immunotherapy for Hepatocellular Carcinoma

Article

作者: Lei, Xiaoyong ; Yang, Xiaoyan ; Huang, Sheng ; Liu, Xiaoyi

Abstract:Hepatocellular carcinoma is the sixth most common tumor and the third leading cause of cancer death worldwide. It ranks fourth in the spectrum of malignant tumor incidence and second in the order of death from major malignant tumors in China. Hepatocellular carcinoma is a complex ecosystem containing non-tumor cells (mainly immune-related cells), and its immunotherapy can stimulate the recognition of specific tumor antigens, inhibit the proliferation of cancer cells, and produce over-memory lymphocytes, which can prevent recurrence. So, immunotherapy of hepatocellular carcinoma is increasingly becoming a research hotspot in liver cancer treatment. With the intensive research in recent years, great progress has been made in immunotherapy for hepatocellular carcinoma, including immune checkpoint inhibitors, pericyte therapy, vaccination, and antiviral therapy. In addition, the study found that the therapeutic effect of combination therapy was enhanced compared to monotherapy. This review summarizes the most prominent immunotherapies currently available for the clinical treatment of patients with HCC and the main opportunities and challenges facing HCC research.

2025-01-01·Joint Bone Spine

Resolution of immune checkpoint inhibitors-induced inflammatory arthritis while maintaining active treatment with checkpoint inhibitors and after its discontinuation: An observational study

Article

作者: Kostine, Marie ; Prey, Sorilla ; Lefort, Felix ; Veillon, Rémi ; Barnetche, Thomas ; Daste, Amaury ; Gerard, Émilie ; Mathieu, Larroquette ; Pham-Ledard, Anne ; Beylot-Barry, Marie ; Ladouceur, Alexandra ; Domblides, Charlotte ; Sionneau, Baptiste ; Gross-Goupil, Marine ; Zysman, Maeva ; Richez, Christophe ; Truchetet, Marie-Elise ; Dutriaux, Caroline ; Schaeverbeke, Thierry

INTRODUCTIONImmune checkpoint inhibitors-induced inflammatory arthritis (ICI-IA) affects about 5% of ICI recipients. We aimed 1) to characterize the resolution of ICI-IA during ICI treatment and after ICI discontinuation and 2) to assess how ICI-IA influences ICI management across time.METHODSAll ICI-treated patients referred to rheumatology at Bordeaux University Hospital were identified and patients with ICI-IA with a follow-up of ≥ 6 months after ICI-IA onset were included. Resolution of ICI-IA was defined by discontinuation of ICI-IA medications without recurrence of ICI-IA symptoms.RESULTSResolution of ICI-IA occurred in 13 of 80 patients (16%) while maintaining active ICI treatment, mainly in patients with polymyalgia rheumatica (PMR)-like clinical presentation (p=0.03). Synovitis was more frequent in those whose ICI-IA persisted throughout ICI treatment. In patients with persistent ICI-IA throughout ICI treatment, 34 (50%) and 47 (70%) resolved at 6- and 12-months post ICI discontinuation, respectively. Reason for terminating ICI was more frequently cancer stable or in remission in those who still had active ICI-IA at 6- and 12- months post ICI discontinuation. Both progression-free survival and overall survival were longer in the groups with active ICI-IA at 6- and 12-months after ICI discontinuation.DISCUSSIONIn this cohort, ICI was safely continued in most patients experiencing ICI-IA. About one sixth of ICI-IA resolved despite maintaining active ICI treatment and allowing ICI-IA treatment discontinuation without recurrence of symptoms, mainly in those with PMR-like presentation. Larger studies are needed to determine predicting factors of resolving ICI-IA to minimize exposure to immunosuppressive treatment.

项与 PX-D26116 相关的新闻（医药）

2024-09-15

·GlobeNewswire-Health Care

IO Biotech Announces Positive Results from Phase 2 Trial of IO102-IO103 in the First-line Treatment of Advanced Head and Neck Cancer

-- Study Meets Overall Response Rate Primary Endpoint, Encouraging Secondary Endpoint Progression-Free Survival Data in Squamous Cell Carcinoma of the Head and Neck Cohort -- -- No New Safety Signals or Added Systemic Safety Concerns Observed -- -- Data Presented at the European Society for Medical Oncology (ESMO) Congress -- Sept. 14, 2024 -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, off-the-shelf, immune-modulating therapeutic cancer vaccines, announced promising data from the Phase 2 basket trial of IO102-IO103, the company’s lead investigational therapeutic cancer vaccine candidate, in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) (IOB-022/KN-D38) at the 2024 ESMO Congress in Barcelona from September 13-17. The presentation contained clinical and biomarker data from a cohort of patients with recurrent or metastatic (advanced) squamous cell carcinoma of the head and neck (SCCHN) with PD-L1 CPS ≥ 20 (PD-L1 high), contributing to the growing body of research supporting the potential clinical benefit of this combination regimen for these patients. The data from 18 efficacy evaluable patients demonstrated: Achievement of the primary endpoint – confirmed 44.4% overall response rate (ORR) in a PD-L1 high population of patients with SCCHN irrespective of HPV status. An encouraging 6.6-month median progression-free survival (PFS). A 66.7% disease control rate (DCR). A safety profile consistent with previously reported data when combined with anti-PD-1 monotherapy. T-cell responses to both IO102 (targeting IDO) and IO103 (targeting PD-L1) were detected after treatment. “These encouraging data further support the potential of IO102-IO103 in combination with pembrolizumab as first-line treatment for patients with recurrent or metastatic SCCHN including HPV-positive and -negative patients,” stated Jonathan Riess, MD, principal investigator of the trial and Director, Thoracic Oncology at the UC Davis Comprehensive Cancer Center. “Given the need for new treatment options that are effective, safe and accessible for head and neck cancer patients, further investigation of this combination should be conducted to build on the findings of this Phase 2 trial.” “With the data we’ve presented from studies in head and neck cancer and in melanoma, evidence is accumulating that the combination of IO102-IO103 with the anti-PD-1 therapy pembrolizumab could be a safe and efficacious first-line treatment for patients with a range of cancers, including those with metastatic and difficult-to-treat disease,” said Qasim Ahmad, MD, Chief Medical Officer of IO Biotech. “Importantly, with mPFS of 6.6 months, more than half of the patients in this trial had over 180 days of progression-free survival. These data are supportive of further investigation of this combination regimen as part of our commitment to transform the lives of cancer patients through our novel therapeutic vaccine.” The Phase 2 basket study (IOB-022/KN-D38; NCT05077709) is a non-comparative, open-label trial to investigate the safety and efficacy of IO102-IO103 in combination with pembrolizumab as a first-line treatment in up to 60 patients with metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥ 50% and recurrent or metastatic SCCHN with PD-L1 CPS ≥ 20. The primary endpoint of the study is overall response rate. Patients enrolled in the study who had at least 2 post-baseline tumor assessments or who discontinued after 2 cycles of study treatment as of the data cut off of August 2, 2024 were considered efficacy evaluable and were included in the ESMO poster presentation. To date, the safety profile observed in this study (OB-022/KN-D38) is consistent with prior studies of IO102-IO103 in combination with checkpoint inhibitors, with no added significant systemic toxicity compared to anti-PD1 monotherapy and low-grade transient injection site reactions reported as the most common treatment related adverse events. The trial has completed enrollment of patients in all cohorts. Data from the non-small cell lung cancer (NSCLC) cohort of this study will also be presented at another medical meeting in the fall. The poster can be found on the “Posters & Publications” page of the IO Biotech website. Details for the presentation are below: Poster Title: A phase 2 trial of the IO102-IO103 vaccine plus pembrolizumab: completed cohort for first line (1L) treatment of advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) Presentation number: 1022P Presenter: Jonathan W. Riess, MD, MS (UC Davis Comprehensive Cancer Center) Date: Saturday, September 14, 2024 Time: 12:00 PM – 1:00 PM CEST IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase (IDO) positive and programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating IO102-IO103 in combination with pembrolizumab as first line treatment in patients with solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating IO102-IO103 in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. IOB-022/KN-D38 (NCT05077709) is a non-comparative, open-label trial to investigate the safety and efficacy of IO102-IO103 in combination with pembrolizumab in first-line advanced cancers in non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103. IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating therapeutic cancer vaccines based on its T-win® platform. The T-win platform is based on a novel approach to cancer vaccines designed to activate T cells to target the immunosuppressive cells in the tumor microenvironment. IO Biotech is advancing its lead cancer vaccine candidate, IO102-IO103, in clinical trials, and additional pipeline candidates through preclinical development. Based on positive Phase 1/2 first line metastatic melanoma data, IO102-IO103, in combination with pembrolizumab, has been granted a breakthrough therapy designation for the treatment of advanced melanoma by the US Food and Drug Administration. IO Biotech is headquartered in Copenhagen, Denmark and has US headquarters in New York, New York. The content above comes from the network. if any infringement, please contact us to modify.

疫苗突破性疗法临床结果

2024-06-18

·BioSpace

CEL-SCI Presents Head & Neck Cancer Data at Iddst Annual Congress in Budapest: Risk of Death Cut in Half for Patients Treated With Multikine in the Target Population

Multikine significantly increases overall survival in patients with low levels of tumor cell PD-L1 expression in contrast to approved checkpoint inhibitors 73% survival for Multikine vs 45% in the control arm at 5 years Statistically significant log rank p = 0.0015 5-year risk of death cut in half from 55% to 27% Hazard ratio = 0.35 (95% CIs [0.19, 0.66]) Working to commence FDA confirmatory Registration Study for Multikine VIENNA, Va.--(BUSINESS WIRE)-- CEL-SCI Corporation (NYSE American: CVM) today announced the Company’s Chief Scientific Officer, Dr. Eyal Talor, delivered a presentation titled “Neoadjuvant Immunotherapy for Head and Neck Cancer: Low Tumor PD-L1 Expression - IT-MATTERS – RCT” at the International Drug Discovery Science & Technology (IDDST) 20th Annual Congress in Budapest, Hungary on Tuesday, June 18, 2024. Dr. Talor presented during the Cancers/Tumors session which he Chaired along with Dr. Elizabeth Tran of Purdue University. This press release features multimedia. View the full release here: (Graphic: Business Wire) Multikine* (Leukocyte Interleukin, Injection) is the first investigational pre-surgical cancer drug intended for use in newly diagnosed locally advanced resectable head and neck cancer. There is extensive affirmative safety and efficacy data from 750 patients who have been treated with Multikine. A randomized, controlled, Phase 3 trial (RCT) in head and neck cancer revealed that Multikine significantly increases overall survival in patients with low levels of tumor cell PD-L1 expression in contrast to checkpoint inhibitors (e.g. Keytruda, Opdivo) which show longer survival benefit in patients with a higher level of tumor cell PD-L1 expression. Tumor cell PD-L1, also known as Programmed Death-Ligand 1, is a protein that plays a crucial role in immune system regulation. It is the target pathway for immune checkpoint inhibitors, a major class of immune-oncology drugs which work by blocking the interaction between tumor cell PD-L1 and the PD-1 receptor on immune effector cells, thereby favoring immune evasion by the tumor. “The survival benefit of Multikine we observed from previous data for the same study population is much higher than that which will be required to be successful in the confirmatory study,” stated Dr. Talor. The presentation may be accessed on CEL-SCI’s website at the following: About CEL-SCI Corporation CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Multikine is designed to help the immune system "target" the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. Multikine (Leukocyte Interleukin, Injection), a true first-line cancer therapy, has been dosed in over 750 patients and received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. Multikine significantly extended life in its target patient population demonstrating a 73% survival rate with Multikine treatment regimen plus standard of Care (SOC) vs. only 45% for SOC without Multikine, at 5 years after treatment, Kaplan-Meier life table log rank p-value 0.0015. Based on this very strong data, the FDA concurred with CEL-SCI’s target patient selection criteria and gave the go-ahead to conduct a smaller, focused, confirmatory Registration Study of 212 patients. CEL-SCI will enroll newly diagnosed treatment naïve locally advanced primary SCC of the head and neck (oral cavity) cancer patients with no lymph node involvement (determined via PET scan) and with low PD-L1 tumor expression (determined via biopsy). Globally, there are approximately 100,000 patients meeting these diagnostic criteria annually. The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2023. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. * Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy. This proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use. View source version on businesswire.com: Contacts Gavin de Windt CEL-SCI Corporation (703) 506-9460 Source: CEL-SCI Corporation Smart Multimedia Gallery Photo (Graphic: Business Wire) Logo View this news release and multimedia online at:

免疫疗法临床3期孤儿药临床结果

2024-06-17

·PRNewswire

Mozart Therapeutics Doses First Cohort of Participants in Phase 1a/b Clinical Trial of MTX-101, in Development for Treatment of Autoimmune Diseases

Study to Evaluate MTX-101 for Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Adults and Patients SEATTLE, June 17, 2024 /PRNewswire/ -- Mozart Therapeutics, a clinical stage biopharmaceutical company focused on the development of CD8 Treg modulators in autoimmune diseases, today announce the dosing of the first cohort of participants in the Company's initial clinical study of MTX-101, a first-in-class CD8 Treg modulator and autoimmune checkpoint inhibitor. "Dosing the first cohort of participants in this Phase 1a/b clinical study with MTX-101 is a significant milestone for Mozart, marking our transition into the clinic and bringing us closer to reaching our goal of changing the treatment paradigm by modifying the course of autoimmune disease in every patient," said Katie Fanning, President and Chief Executive Officer of Mozart Therapeutics. "In autoimmune disease, CD8 Treg fail to recognize and eliminate pathogenic or self-reactive CD4 T cells, resulting in downstream proinflammatory events and perpetuation of tissue destruction. The aim of MTX-101 is to selectively target a fundamental cause of immune dysregulation and restore immune homeostasis in autoimmune disease" added Ms. Fanning. The Phase 1a portion of the study (NCT06324604) is a single and multiple ascending dose escalation study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MTX-101 in healthy adults. The Phase 1b is a prospective, multi-center, randomized, double-blind, placebo-controlled trial to evaluate safety, PK, PD, and disease-specific biomarkers in patients with type 1 diabetes mellitus or celiac disease. "While the goal of this trial is to carefully characterize the profile of a novel approach to restoring immune homeostasis, we also recognize the urgent need for safer, more effective targeted approaches to preventing and treating chronic debilitating autoimmune diseases. Following completion of the Phase 1a portion, we expect to generate proof-of-mechanism data across two mechanistically and clinically different autoimmune diseases, and hopefully demonstrate the potential for CD8 Treg biology to be broadly relevant," said Dr. Jason Chien, Chief Medical Officer at Mozart. About MTX-101 MTX-101 is a bispecific antibody targeting inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This autoimmune checkpoint inhibitor aims to restore the intrinsic functions of regulatory CD8 T cells, acting early in the autoimmune disease process to suppress and eliminate pathogenic cells, halt downstream inflammation, and prevent tissue destruction. About Mozart Therapeutics Mozart Therapeutics is focused on developing first-in-class disease-modifying therapies for autoimmune diseases, utilizing a novel approach to restoring immune system function by targeting the CD8 T regulatory network. The company is headquartered in Seattle, WA. For more information, visit and follow the company on LinkedIn @Mozart–tx.com. SOURCE Mozart Therapeutics

临床1期免疫疗法临床2期

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