Putting lung cancer cells on the RADar for immunotherapy

Project Details

Description

In recent years, immunotherapy reached unprecedented survival outcomes for advanced non-small cell lung cancer (NSCLC) patients. Unfortunately, this only holds true for about 25% of them. An important underlying reason can be found in the lack of tumor antigenicity due to paucity of immunogenic antigens and/or their aberrated presentation by Major Histocompatibility Complex I (MHC-I), hampering effective cytotoxic T lymphocyte (CTL) stimulation.

Inspired by the quote; “Never let a good crisis go to waste”, I propose to make use of the SARS-CoV-2 pandemic to revolutionize the treatment paradigm for lung cancer. The latter is rationalized by the potential to sensitize tumor cells to Spike glycoprotein (S-GP) specific memory T cells, present in most previously infected
and/or vaccinated beings. Specifically, I aim to design RADars; replication-defective adenoviral vectors that drive the expression of S-GP together with the MHC-l stabilizing molecule β2-microglobulin (β2M) in tumor cells. To enhance their biosafety profile, gene expression will be restricted by a tumor specific promotor (hTERT or RAD51). Further, the RADar project aims to deliver clinically relevant human results by applying state-of-the- art immunological assays. In first instance, I will use human MAGE-A1+ NSCLC spheroids and the MAGE-A1-
specific CTL89 clone, maintained and evaluated within a biophysiological relevant microfluidics device and orthotopic xenograft model. Next, I will assess if RADar transduction of NSCLC patient-derived tumor cells can invigorate autologous T cells. As such, the RADar project holds great potential to enhance the sobering
outcomes to immunotherapy for a broad range of cancer patients.
AcronymANI327
StatusFinished
Effective start/end date1/11/2231/10/23

Keywords

  • RADar
  • Immunotherapy

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