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Topics {✒️}

month download article/chapter messenger rna-based vaccines small-cell lung cancer immunostimulating single-stranded rna cell-intrinsic tlr7 signaling lotta von boehmer single-dose cyclophosphamide associates antigen-specific immune responses specific t-cell response vivo ifn-gamma elispot alexander knuth reports article cancer immunology central ethics committee hiv klinikum der resected mage-a3-positive mage-a3 cancer immunotherapeutic long-term survival correlates /iia dose-escalation trial therapeutic cancer vaccines squamous cell carcinoma lung cancer reveals combination therapies supporting gure ao mariola fotin-mleczek & sven von der mf induce clinical benefit full article pdf provide antitumor activity medizinische klinik ii systemic rna delivery advanced squamous-cell immune cell populations privacy choices/manage cookies mrna-based immunotherapy article sebastian treating lung cancer hellmann md dose escalation trial cv9201 dose levels mariola fotin-mleczek multiple peptides derived melan-a-specific tumor-initiating cells tumor antigen determines elispot assay performance improved therapeutic effect therapeutic epitope-peptides cell populations revealed cd4+ immune responses spontaneous germinal centers

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         headline:A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer
         description:CV9201 is an RNActive®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400–1600 µg of mRNA). The primary objective of the trial was to assess safety. Secondary objectives included assessment of antibody and ex vivo T cell responses against the five antigens, and changes in immune cell populations. All CV9201 dose levels were well-tolerated and the recommended dose for phase IIa was 1600 µg. Most AEs were mild-to-moderate injection site reactions and flu-like symptoms. Three (7%) patients had grade 3 related AEs. No related grade 4/5 or related serious AEs occurred. In phase IIa, antigen-specific immune responses against ≥ 1 antigen were detected in 63% of evaluable patients after treatment. The frequency of activated IgD+CD38hi B cells increased > twofold in 18/30 (60%) evaluable patients. 9/29 (31%) evaluable patients in phase IIa had stable disease and 20/29 (69%) had progressive disease. Median progression-free and overall survival were 5.0 months (95% CI 1.8–6.3) and 10.8 months (8.1–16.7) from first administration, respectively. Two- and 3-year survival rates were 26.7% and 20.7%, respectively. CV9201 was well-tolerated and immune responses could be detected after treatment supporting further clinical investigation.
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            mRNA
            Non-small cell lung cancer
            Immunomonitoring
            Clinical trial
            CV9201
            Oncology
            Immunology
            Cancer Research
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      headline:A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer
      description:CV9201 is an RNActive®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400–1600 µg of mRNA). The primary objective of the trial was to assess safety. Secondary objectives included assessment of antibody and ex vivo T cell responses against the five antigens, and changes in immune cell populations. All CV9201 dose levels were well-tolerated and the recommended dose for phase IIa was 1600 µg. Most AEs were mild-to-moderate injection site reactions and flu-like symptoms. Three (7%) patients had grade 3 related AEs. No related grade 4/5 or related serious AEs occurred. In phase IIa, antigen-specific immune responses against ≥ 1 antigen were detected in 63% of evaluable patients after treatment. The frequency of activated IgD+CD38hi B cells increased > twofold in 18/30 (60%) evaluable patients. 9/29 (31%) evaluable patients in phase IIa had stable disease and 20/29 (69%) had progressive disease. Median progression-free and overall survival were 5.0 months (95% CI 1.8–6.3) and 10.8 months (8.1–16.7) from first administration, respectively. Two- and 3-year survival rates were 26.7% and 20.7%, respectively. CV9201 was well-tolerated and immune responses could be detected after treatment supporting further clinical investigation.
      datePublished:2019-02-15T00:00:00Z
      dateModified:2019-02-15T00:00:00Z
      pageStart:799
      pageEnd:812
      sameAs:https://doi.org/10.1007/s00262-019-02315-x
      keywords:
         Active cancer immunotherapy
         mRNA
         Non-small cell lung cancer
         Immunomonitoring
         Clinical trial
         CV9201
         Oncology
         Immunology
         Cancer Research
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                  name:Tumorgenetik Bonn
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            name:Helga Bernhard
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