Clinical advances of mRNA vaccines for cancer immunotherapy

Med, Journal Year: 2025, Volume and Issue: 6(1), P. 100562 - 100562

Published: Jan. 1, 2025

Language: Английский

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Unveiling the Promise: Navigating Clinical Trials 1978–2024 for PDAC

Cancers, Journal Year: 2024, Volume and Issue: 16(21), P. 3564 - 3564

Published: Oct. 23, 2024

Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one the most difficult cancers to diagnose and treat effectively. Although there have been improvements in 5-year overall survival rate, it is still very low at 12.5%. The limited efficacy current therapies, even when PDAC detected early, underscores aggressive nature disease urgent need for more effective treatments. Clinical management relies heavily on a repertoire therapeutic interventions, highlighting significant gap between research efforts available Over 4300 clinical trials or are currently investigating different treatment modalities diagnostic strategies PDAC, including targeted immunotherapies, precision medicine approaches. These aim develop treatments improve early detection methods through advanced imaging techniques blood-based biomarkers. This review seeks categorize analyze PDAC-related across various dimensions understand why so few chemotherapeutic options patients despite numerous being conducted. aims provide comprehensive nuanced understanding landscape trials, with overarching goal identifying opportunities accelerate progress drug development patient outcomes fight against this devastating disease.

Language: Английский

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Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Nov. 6, 2024

Abstract Background A limitation of approved oncolytic viruses is their requirement for intratumoral (i.t.) injection. TILT-123 (igrelimogene litadenorepvec, Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) a chimeric adenovirus suitable intravenous (i.v.) delivery due to its capsid modification and dual selectivity devices. It armed with tumor necrosis alpha interleukin-2 promoting T-cell activation lymphocyte trafficking tumors, thereby enhancing the antitumor immune response. Here, we present findings after single i.v. administration in three phase I dose escalation clinical trials. Methods Patients advanced solid tumors initially received ranging from 3 × 10 9 4 12 viral particles (VP). Blood was collected at baseline, 1, 16, 192 h (7 days) post-treatment bioavailability serum analysis. Tumor biopsies were prior treatment 7 days analysis presence immunological effects. did not receive any other cancer therapies during this period. Results Across all trials (TUNIMO, TUNINTIL, PROTA), 52 total patients treated TILT-123. Overall, found be well-tolerated, no dose-limiting toxicities observed. Post-treatment showed expression genes, proteins or DNA, changes cell infiltration baseline. Increased virus lead increased detection tumors. Median overall survival longer confirmed (280 versus 190 days, p = 0.0405). Conclusion demonstrated safety significant immunomodulation following administration, warranting further investigation. Trial registrations TUNIMO—NCT04695327. Registered January 2021, https://clinicaltrials.gov/study/NCT04695327 . TUNINTIL—NCT04217473. 19 December 2019, https://clinicaltrials.gov/study/NCT04217473 PROTA—NCT05271318. February 2022, https://clinicaltrials.gov/study/NCT05271318

Language: Английский

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Updates in Immunotherapy for Pancreatic Cancer

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(21), P. 6419 - 6419

Published: Oct. 26, 2024

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective therapeutic options. Due to a variety of cancer cell-intrinsic factors, including KRAS mutations, chemokine production, and other mechanisms that elicit dysregulated host immune response, PDAC often characterized by poor infiltration immune-privileged fibrotic stroma. As understanding the tumor microenvironment (TME) evolves, novel therapies are being developed target immunosuppressive mechanisms. Immune checkpoint inhibitors have efficacy when used alone or radiation. Combinations therapies, along chemotherapy chemoradiation, demonstrated promise in preclinical early clinical trials. Despite dismal response rates for immunotherapy metastatic PDAC, neoadjuvant somewhat encouraging, suggesting incorporation treatment should be earlier disease course. Precision therapy may informed advances transcriptomic sequencing can identify immunophenotypes, allowing more appropriate selection each individual patient. Personalized antigen-specific increasing topic interest, adjuvant using personalized mRNA vaccines prevent recurrence. Further development will need balance precision generalizability cost.

Language: Английский

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Exploring the role of antigen-presenting cancer-associated fibroblasts and CD74 on the pancreatic ductal adenocarcinoma tumor microenvironment

Medical Oncology, Journal Year: 2024, Volume and Issue: 42(1)

Published: Nov. 25, 2024

Language: Английский

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