Breaking the Silence: Alithea Bio and CHOP Unveil “HLA-Shuttle” to Target Immunologically Cold Tumors

We are thrilled to announce our latest collaborative publication in Science Advances, titled: “HLA-Shuttle: A system for enhancing antigen presentation in immunologically cold tumors.”
This research—a partnership between Alithea Bio and the Children’s Hospital of Philadelphia (CHOP)—introduces a revolutionary technology designed to tackle one of the greatest challenges in immunotherapy: “immunologically cold” tumors.
The Challenge: Invisible Tumors
For the immune system to destroy a cancer cell, it must first “see” it. This visibility depends on HLA-I molecules, which act as windows into the cell, presenting peptide antigens to T-cells. However, many aggressive cancers, such as neuroblastoma, have evolved to “pull the blinds”—they down-regulate their HLA-I machinery, effectively hiding from the immune system and becoming resistant to current immunotherapies.
The Innovation: The HLA-Shuttle
Led by experts including Dr. Nikolaos G. Sgourakis (CHOP) and Alithea Bio’s own Tim Fugmann and Trendelina Rrustemi, the team developed the HLA-Shuttle.
This system uses engineered components of the HLA-I processing machinery to:
Restore and stabilize HLA-I presentation on the cell surface.
Extend the lifetime of these molecules, ensuring the immune system has a longer window to detect them.
Reveal hidden targets: By restoring this pathway in neuroblastoma cells, the team was able to identify multiple new tumor-associated antigens (TAAs) that were previously invisible.
Alithea’s Role: Precision Immunopeptidomics
Alithea Bio played a critical role in this breakthrough by applying our world-leading expertise in immunopeptidomics. Using our high-sensitivity mass spectrometry and advanced bioinformatics, we helped identify the specific peptide antigens that were successfully brought back to the surface by the HLA-Shuttle.
This work proves that by “re-opening the window” of antigen presentation, we can identify a new generation of therapeutic targets for childhood cancers and other hard-to-treat solid tumors.
Read the Full Publication
We are proud to see this work published in Science Advances and look forward to how the HLA-Shuttle will pave the way for more effective, safer T-cell therapies.
Read the full paper here: https://www.science.org/doi/10.1126/sciadv.aeb0821