A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.

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.

[Clinical comparison of isoflurane and sevoflurane anaesthesia in the gerbil (Meriones unguiculatus)]. / Klinischer Vergleich einer Iso- und Sevofluranmononarkose beim Gerbil (Meriones unguiculatus).

The objective of this study was a comparison of the volatile anaesthetics isoflurane and sevoflurane in terms of their clinical effects in gerbils (Meriones unguiculatus) (n=12 each). Induction of anaesthesia was performed in a body chamber with an anaesthetic concentration of 4.0 Vol.% at an oxygen flow of 500 ml/min for isoflurane and 8.0 Vol.% at an oxygen flow of 1000 ml/min for sevoflurane, respectively. Anaesthesia was maintained via nose cone with an anaesthetic concentration of 2.8 to 3.2 Vol.% at an oxygen flow of 200 ml/min for isoflurane and 5.0 to 5.2 Vol.% at an oxygen flow of 400 ml/min for sevoflurane. Those anaesthetic concentrations ensured reflex status conform with surgical tolerance. In spite of its higher blood-gas coefficient induction time was slightly faster for isoflurane. Recovery time was significantly longer in the isoflurane group than it was in the sevoflurane group. Both inhalants caused respiratory depression. Respiratory rate was lower in sevoflurane animals compared to isoflurane. The animals were positioned on a heating pad immediately after induction, thus a decrease of the body temperature could be prevented. Both inhalants can be recommended for usage in gerbils. Sevoflurane showed no clinical benefit compared to isoflurane.