/ News, Research
Two TANDEM Grants with a strong focus on translational research to the Department of Biomedicine (Jeker Lab and Bentires-Alj Lab)
We are delighted that this year, the ISREC Foundation awarded two of our research group leaders with a TANDEM grant, enabling scientists and clinicians to work together to translate from basic research findings into novel cancer therapies or to identify new biomarkers. Among the seven awarded research teams, Prof. Lukas Jeker & Prof. Andreas Holbro (USB) and Prof. Mohamed Bentires Alj together with Prof. Walter Weber (USB) will address a clinically relevant question from two perspectives: understanding the underlying molecular mechanisms and directly enhancing cancer patient care.
Acute myeloid leukemia (AML) is a rapidly progressing, deadly disease if untreated, with an increasing incidence as the population ages. Despite aggressive treatments like chemotherapy and allogeneic stem cell transplantation (HCT), many patients relapse, highlighting the need for innovative therapies. Chimeric antigen receptor (CAR) T cells have transformed treatment in lymphoid malignancies, but similar success in AML has been challenging due to the lack of AML-specific antigens and the complex tumor environment. CD33, a receptor found on most AML cells, has been a target, but previous therapies like gemtuzumab ozogamicin (GO) faced safety concerns and long-term efficacy. A novel approach involves engineering CD33 knock-out hematopoietic stem and progenitor cells (HSPCs) to protect healthy cells during targeted therapy. Preliminary trials show safety, but long-term effects remain unknown. The USB team aims to go one step further by preserving CD33 expression and function, while still protecting the healthy cells. At the USB, the interdisciplinary Innovation Focus Cell Therapy (IF CT) team, including Profs. Holbro, Jeker, Khanna, and Läubli, is advancing cell and gene therapy trials. In the awarded research program “Toward a CD33-directed Shielded Cell/Immunotherapy Pair First-in-Human clinical trial for Acute Myeloid Leukemia”, their strategic goal is to generate preclinical data for a first-in-human trial using these next-generation CD33-engineered HSPCs combined with anti-CD33 CAR T cells, aiming to improve survival outcomes for AML patients.
Breast cancer is the leading cause of cancer death in women and 2.6 million patients are diagnosed with the disease annually. The survival rates for breast cancer have improved over the last decades, but more than 650,000 lives (1500 in Switzerland) are lost annually because of therapy-resistant metastases. The majority of patients with hormone receptor-positive breast cancer have a good prognosis and respond well to endocrine therapy. Unfortunately, in a subset of patients, therapy is thwarted by emerging resistance which leads to tumor recurrence and an inexorable downhill course. Clearly, there is a large unmet clinical need to uncover additional therapies for breast cancer patients that are resistant to endocrine and targeted therapies. The immune system influences disease progression and treatment response. However, the tumor immune microenvironment is not explicitly accounted for in the clinically validated tests used to predict risk of recurrence and therapy response in hormone receptor-positive breast cancer. In their project: «Immune mapping of tumor draining lymph nodes to predict therapy response and optimize immunotherapy-based combinations in hormone receptor positive breast cancer», Prof. Dr. Mohamed Bentires-Alj as the scientist engaged in basic research and in charge of the translational aspects of the TAXIS trial and Prof. Dr. Walter Paul Weber, as the clinical scientist who leads the TAXIS trial (NCT03513614), aim to assess the cellular composition and spatial organization in the primary tumor and tumor draining lymph nodes in hormone receptor-positive breast cancer patients. It will also evaluate its predictive value for response to therapy. The results of such studies will help optimise treatment for hormone receptor-positive breast cancer patients.
We congratulate all the teams involved and wish them success with their visionary projects that underscore our commitment to translating groundbreaking research into real-world clinical solutions.
New biomarkers may predict therapeutic response in breast cancer – Prof. Mohamed Bentires-Alj and Prof. Walter Weber