TY  - JOUR
A1  - Czysch, Christian
A1  - Medina‐Montano, Carolina
A1  - Zhong, Zifu
A1  - Fuchs, Alexander
A1  - Stickdorn, Judith
A1  - Winterwerber, Pia
A1  - Schmitt, Sascha
A1  - Deswarte, Kim
A1  - Raabe, Marco
A1  - Scherger, Maximilian
A1  - Combes, Francis
A1  - De Vrieze, Jana
A1  - Kasmi, Sabah
A1  - Sandners, Niek N.
A1  - Lienenklaus, Stefan
A1  - Koynov, Kaloian
A1  - Räder, Hans‐Joachim
A1  - Lambrecht, Bart N.
A1  - David, Sunil A.
A1  - Bros, Matthias
A1  - Schild, Hansjörg
A1  - Grabbe, Stephan
A1  - De Geest, Bruno G.
A1  - Nuhn, Lutz
T1  - Transient Lymph Node Immune Activation by Hydrolysable Polycarbonate Nanogels
JF  - Advanced Functional Materials
N2  - The development of controlled biodegradable materials is of fundamental importance in immunodrug delivery to spatiotemporally controlled immune stimulation but avoid systemic inflammatory side effects. Based on this, polycarbonate nanogels are developed as degradable micellar carriers for transient immunoactivation of lymph nodes. An imidazoquinoline‐type TLR7/8 agonist is covalently conjugated via reactive ester chemistry to these nanocarriers. The nanogels not only provide access to complete disintegration by the hydrolysable polymer backbone, but also demonstrate a gradual disintegration within several days at physiological conditions (PBS, pH 6.4–7.4, 37 °C). These intrinsic properties limit the lifetime of the carriers but their payload can still be successfully leveraged for immunological studies in vitro on primary immune cells as well as in vivo. For the latter, a spatiotemporal control of immune cell activation in the draining lymph node is found after subcutaneous injection. Overall, these features render polycarbonate nanogels a promising delivery system for transient activation of the immune system in lymph nodes and may consequently become very attractive for further development toward vaccination or cancer immunotherapy. Due to the intrinsic biodegradability combined with the high chemical control during the manufacturing process, these polycarbonate‐based nanogels may also be of great importance for clinical translation.
KW  - biodegradable
KW  - immunodrug delivery
KW  - lymph nodes
KW  - nanogels
KW  - polycarbonates
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287255
VL  - 32
IS  - 35
ER  - 
TY  - JOUR
A1  - Haist, Maximilian
A1  - Stege, Henner
A1  - Lang, Berenice Mareen
A1  - Tsochataridou, Aikaterini
A1  - Salzmann, Martin
A1  - Mohr, Peter
A1  - Schadendorf, Dirk
A1  - Ugurel, Selma
A1  - Placke, Jan-Malte
A1  - Weichenthal, Michael
A1  - Gutzmer, Ralf
A1  - Leiter, Ulrike
A1  - Kaatz, Martin
A1  - Haferkamp, Sebastian
A1  - Berking, Carola
A1  - Heppt, Markus
A1  - Tschechne, Barbara
A1  - Schummer, Patrick
A1  - Gebhardt, Christoffer
A1  - Grabbe, Stephan
A1  - Loquai, Carmen
T1  - Response to first-line treatment with immune-checkpoint inhibitors in patients with advanced cutaneous squamous cell carcinoma: a multicenter, retrospective analysis from the German ADOReg registry
JF  - Cancers
N2  - Cutaneous squamous cell carcinoma (cSCC) is a common malignancy of the skin and has an overall favorable outcome, except for patients with an advanced stage of the disease. The efficacy of checkpoint inhibitors (CPI) for advanced cSCC has been demonstrated in recent clinical studies, but data from real-world cohorts and trial-ineligible cSCC patients are limited. We retrospectively investigated patients with advanced cSCC who have been treated with CPI in a first-line setting at eight German skin cancer centers registered within the multicenter registry ADOReg. Clinical outcome parameters including response, progression-free (PFS) and overall survival (OS), time-to-next-treatment (TTNT), and toxicity were analyzed and have been stratified by the individual immune status. Among 39 evaluable patients, the tumor response rate (rwTRR) was 48.6%, the median PFS was 29.0 months, and the median OS was not reached. In addition, 9 patients showed an impaired immune status due to immunosuppressive medication or hematological diseases. Our data demonstrated that CPI also evoked tumor responses among immunocompromised patients (rwTRR: 48.1 vs. 50.0%), although these responses less often resulted in durable remissions. In line with this, the median PFS (11 vs. 40 months, p = 0.059), TTNT (12 months vs. NR, p = 0.016), and OS (29 months vs. NR, p < 0.001) were significantly shorter for this patient cohort. CPI therapy was well tolerated in both subcohorts with 15% discontinuing therapy due to toxicity. Our real-world data show that first-line CPI therapy produced strong and durable responses among patients with advanced cSCC. Immunocompromised patients were less likely to achieve long-term benefit from anti-PD1 treatment, despite similar tumor response rates.
KW  - advanced cutaneous squamous cell carcinoma
KW  - checkpoint inhibitor therapy
KW  - cemiplimab
KW  - immunosuppression
KW  - response durability
KW  - real-world data
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297506
SN  - 2072-6694
VL  - 14
IS  - 22
ER  -