NEWS
Post-infection SARS-CoV-2 vaccination is associated with fewer gastrointestinal symptoms in long COVID-19
5 Feb 2024
Congratulations to Christoph for his first paper as corresponding author and Claudia for her first publication now published in npj Vaccines.
They analyzed serological markers in 540 individuals with or without post-COVID-19 condition (PCC; "long COVID-19") and looked especially on association with vaccination status. They found that post-infection vaccination with one or more doses does not increase symptom burden or any pro-inflammatory marker associated with PCC. Vaccination with mRNA vaccines or seasonal influenza vaccine in control cohorts did also not result in any PCC-like persisting symptoms.
Importantly, they observed that patients with ongoing PCC symptoms less often reported gastrointestinal symptoms when receiving one or two doses of a SARS-CoV-2 mRNA vaccine. This was associated with substantially lower plasma levels of IL-1 family cytokines (IL-1beta/IL-18) known players in SARS-CoV-2 clearance within the intestine.
This work further corroborates the safety of SARS-CoV-2 vaccines and also demonstrates the potential benefit for a subset of patients with PCC.
IGLV3-21-R110 targeting CAR T cells published
2 Feb 2024
We are very happy that our manuscript on IGLV3-21-R110-targeting CAR T cells is now published in Nature Communications.
The IGLV3-21-R110 light chain mutation is found in 10-15% of all patients with chronic lymphocytic leukemia (CLL) and defines a patient subset with aggressive disease. This point mutation is of particular interest since it generates an antigen receptor configuration that acts as driver of neoplastic transformation.
We now developed CAR T cells targeting this oncogenic light chain and provide provide proof-of-concept for the targeting of a single point mutation using CAR T cells. Notably, we demonstrate the lack of CAR T-mediated cytotoxicity towards healthy B cells, which is a major advancement as compared to other CAR T approaches that eradicate the complete B cell compartment. These results underpin the potential value of such precision approaches and warrant clinical investigations.
Huge congratulations to the first authors Florian Märkl from Sebastian Kobold's lab at TUM in Munich and Christoph for this achievement! Very special thanks to Sebastian for this joint effort! Thanks also to Nicholas Chiorazzi (New York), Obinna Chijioke (Basel/Zurich), Susana Minguet (Freiburg), Heinz Läubli (Basel) and Michael Hudecek (Würzburg).
SARS-CoV-2-associated T cell infiltration in the central nervous system
31 Jan 2024
Congratulations to Malte Mohme from UKE in Hamburg and Christoph for their recent publication in Clinical & Translational Immunology on SARS-CoV-2-associated T cell infiltration in the brain.
They analyzed eight different brain regions from deceased patients with COVID-19 and found T cell infiltration especially in the olfactory bulb, medulla and cerebellum. These were mainly CD8+ T cells exhibiting a perivascular infiltration pattern.
The immunogenetic analysis of these T cells revealed high homology to known clonotypes with SARS-CoV-2 spike (44%), ORF1ab (21%), NCP (17%) and NSP3 (10%) reactivity.
Future studies are needed to define the precise role of these infiltrating T cells for COVID-19-related neuropathology and potential long-term consequences on patients' cognitive and mental health.
RAP trial published
24 Jan 2024
The results from the AIO RAP trial with Peter Thus-Patience are now published at JAMA Network Open.
Gastric cancer is responsible for 1 million new cancer diagnoses every year and ranks fourth for cancer-related mortality worldwide. Most patients are diagnosed at late stages with metastatic disease and are amenable only to palliative systemic therapy.
The AIO RAP trial was desigend to compare the efficacy and tolerability of ramucirumab and paclitaxel combined with the checkpoint inhibitor avelumab (PDL-1 inhibitor) in the second-line treatment of patients with esophagogastric adenocarcinoma.
This study demonstrates that the combination of ramucirumab, avelumab, and paclitaxel is well tolerated and highly effective in the second-line treatment of a patient population with heavy pretreatment. In addition, patients with low levels of cfDNA and high T cell richness ware associated with favorable outcomes, while high levels of cfDNA were associated with a significantly shorter overall survival. These findings suggests cfDNA and T cell repertoire richness as potential markers to select patients for therapy.
Best Abstract Award for Christoph
5 Dec 2023
Congratulations to Christoph for his fantastic talk on targeting high-risk IGLV3-21-R110 positive CLL patients using point mutation-specific CAR T cells at this year`s SOHC congress in Basel and for winning the prize of SOHC and SSMO for best abstract in experimental hematology and oncology - well done!!
Preliminary data available as preprint at bioRxiv - check out!
New study from the lab characterizes immune signatures of variant syndromes of primary biliary cholangitis and autoimmune hepatitis
26 April 2023
We are excited to share our new study on the (patho)immunology of variant syndromes of PBC and AIH.
We found that immunogenetic features of B and T cells were good general separators for autoimmune liver disease but less robust for the individual disease subset. However, plasma profiling revealed that the soluble forms of CD25, LAG-3, CD86, and Tim-3 may represent important discriminators between AIH and PBC that could be used to complement established clinical and laboratory parameters such as liver function tests, autoantibodies and Ig levels.
Link to the study published in Hepatology communications.
Mascha Binder is now head of Medical Oncology at University Hospital Basel
01 April 2023
We are very happy to announce that Mascha was appointed Professor of Medical Oncology at the Faculty of Medicine at the University Basel and now also heads the Medical Oncology at the University Hospital of Basel.
The Binder Lab is very proud and excited to continue our work at the Department of Biomedicine soon!
Link to the press release of the University Basel.
Results from the INTEGA study are published in JAMA Oncology
23 June 2022
The results from the AIO INTEGA trial with Alex Stein are now published at JAMA Oncology.
Gastric cancer can remain undetected for a long time because of the often non-specific symptoms in the early stages thus complicating therapy when the cancer is diagnosed in advanced stages. For HER2-positive esophagogastric adenocarcinomas, the current standard of care is the combination of the HER2 antibody trastuzumab and chemotherapy with an average survival of 15 months after diagnosis.
The AIO INTEGA trial was desigend to compare HER2 antibody therapy and potent immuno-therapy (nivolumab and ipilimumab) with the current standard of care plus nivolumab. While the first regimen showed comparable results to the current standard of care, patients in the second group lived an average of 22 months - 7 months longer than when treated without the use of immunotherapy.
This study demonstrates that immunotherapy as addition to the previous standard of care has a positive impact on disease progression and can prolong the survival of patients with HER2-positive gastric cancer.
Our study on post-acute sequelae of COVID-19 (PASC) is now published
21 June 2022
Data from the COVID-19 module of the DigiHero trial addressing post-acute sequelae of COVID-19 (PASC) is now published in Cell Reports Medicine.
It has become increasingly clear that in a substantial number of COVID-19 patients who cleared the underlying SARS-CoV-2 infection, severe health impairments can persist for months. The pathophysiology of PASC ("longCOVID") is still largely unknown and may depend on acute severity and course of COVID-19.
By using a digital epidemiology approach including blood sampling, we show that PASC persists in up to 60% of patients with mild COVID-19 up to 24 months. We also found that PASC is associated with persistent elevation of IL-1β, IL-6 and TNF plasma levels.
Single-cell RNA sequencing analyses of samples from acute COVID-19 suggest that these cytokine levels are potentially secreted from overactivated monocytes/macrophages.
New publication on B cell maturation after SARS-CoV-2 mRNA vaccination
09 May 2022
The first data from the DigiHero is now officially published in Frontiers in Immunology.
We tracked B cells from individuals participating in the DigiHero study through their vaccination series including a third "booster" shot.
The percentage of antigen experienced SARS-CoV-2-specific B cells was low after the first two vaccinations but evolved over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity.
These findings may explain why the third, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron.
For more info on the DigiHero trial click here.
Welcome Denis!
01 April 2022
The Binderlab welcomes its newest member Denis Owczarek!
Denis has lots of academic and industry experience in antibody discovery and production.
We are really happy that he will help us to develop new CAR T cells.
Happy new year 2022
01 January 2022
The Binderlab wishes all of you and your friends and families a happy new year and a good start into 2022!
We have some big plans and are looking forward for the things to come.
Meanwhile, we celebrate this with a little gift to ourseleves and finally launch this website.