Thesis supervisor: Árpád Szöőr
Location of studies (in Hungarian): UD Department of Biophysics and Cell Biology Abbreviation of location of studies: DEBSI
Description of the research topic:
HER2-targeted monoclonal antibodies improve the outcome for advanced breast cancer patients; however, a great percentage of patients experience tumor relapse despite persistent antigen expression. Overexpression of CD44/hyaluran and MUC4 matrix components results in reduced binding of trastuzumab and is clinically associated with poor prognosis. Immune cell therapy with adoptively transferred HER2 specific CAR T cells is an engaging option to improve outcomes for patients with advanced trastuzumab resistant HER2 positive cancer. In our preclinical trial, HER2-specific CAR T cells recognized and efficiently killed trastuzumab resistant JIMT-1 and MDA-HER2 xenograft tumors. However, in human clinical trials serious side effects and impracticable production have emerged as potential limitations. We believe that natural killer cells can equivalently substitute T cells as effectors and at the same time could
overcome these limitations. Thus, in this project, we propose to generate a unique and novel cell therapy platform, a CD44/HER2 TANK (T cell activating NK cell). These cells are created from CRISPR/Cas9 gene edited primary human NK cells that do not express inhibitory receptors, specifically engage the HER2 tumor antigen, and redirect tumor infiltrating lymphocytes to recognize and kill CD44 positive tumor cells. In addition to creating this innovative platform, which can consecutively be adapted to other tumors and their specific antigens, the planned experiments will help us understand the suppressor mechanisms behind NK cell exhaustion. The mechanistic information gained from the project further improves CAR therapies and contributes to the development of novel approaches.
Required language skills: English intermediate level Number of students who can be accepted: 1
Deadline for application: 2021-11-15
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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