Fostering The Design of Innovative Cell Therapies to Existing Immunotherapies for Non-Responders

Research conducted by VHIO's Alena Gros suggests a modern, less intrusive approach to detecting killer T lymphocytes in patients with low mutational burden gastrointestinal tumors that are refractory to authorized immune-based therapies.

Killer T cells found in blood that can hone on mutations expressed in cancer cells pave the way for an effective and customized avenue of therapy.

In today’s current era of precision medicine against cancer, we are increasingly witnessing how research is successfully potentiating and personalizing immunotherapy to more effectively unleash the power of the immune system in a greater number of patients to attack disease. Despite such progress, much work still needs to be done to better predict those patients who would be most likely benefit from them, extend their promise to more patients as well as tumor types – either as monotherapy, or, most likely in combination. “As importantly, we must pursue new therapeutic directions for those patients who are refractory to these novel treatments,” said Alena Gros, Principal Investigator of VHIO’s Tumor Immunology & Immunotherapy Group, and lead and senior author of a study published open access this week in The Journal of Clinical Investigation*.

This study, performed in partnership with Steven A. Rosenberg at the National Cancer Institute (NCI-NIH, Bethesda, USA), an internationally renowned trailblazer of immunotherapy for cancer, along with other investigators at the Robert W. Franz Cancer Center (Portland, USA) and the Karolinska Institute (Stockholm, Sweden), is an important step forward in the search for alternative treatment applications.

Specifically, those patients with high mutational burden gastrointestinal tumors, so-called' hot' tumors, are a potential immunotherapy problem. In a limited number of patients with cold tumors, novel cell therapies focused on administering killer T cells that can identify neoantigens have shown promising antitumor activity.


Such results are breaking new ground in the field by encouraging the design of these therapies to potentially provide new hope to patients with metastatic disease who do not respond to approved cancer immunotherapy treatment. In addition, researchers identified a less invasive, blood-based approach for detecting, measuring, and monitoring neoantigens lymphocytes in advanced gastrointestinal cancers including pancreas, gastroesophageal, bile duct, colon, and rectum.

While we did not expect to find killer T lymphocytes in the blood of these patients with cold tumors, with low mutational burden, we have now shown that we can identify and select these cells in blood, which will facilitate and spur the future development of pioneering and personalized cell therapies by liquid biopsy,” noted Alena Gros.

 “It is thanks to our strong collaboration with the BBVA Foundation, one of VHIO’s patrons, that we launched our Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI). This institutional program seeks to advance agents that inhibit checkpoint regulation of the immune system, decipher mechanisms of resistance and response to these therapies, and prioritize the early development of those agents showing most promise. One of our major objectives is to generate novel cell therapies for the more effective treatment of cancer patients,” she concluded.

This study will promote the identification of neoantigen-specific T lymphocytes derived from blood towards ultimately offering a new array of personalized and more promising anti-cancer immunotherapeutic for these patients.

This work was supported by the BBVA Foundation through the BBVA-VHIO Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), as well as the Instituto de Salud Carlos III (ISCIII) – Carlos III Institute of Health, and FERO Foundation. We also acknowledge and gratefully thank the CELLEX Foundation for VHIO’s state-of-the-art research facilities and scientific equipment.


*Alena Gros, Eric Tran, Maria R. Parkhurst, Sadia Ilyas, Anna Pasetto, Eric M. Groh, Paul F. Robbins, Rami Yossef, Andrea Garcia-Garijo, Carlos A. Fajardo, Todd D. Prickett, Li Jia, Jared J. Gartner, Satyajit Ray, Lien Ngo, John R. Wunderllich, James C. Yang, and Steven A. Rosenberg. Recognition of human gastrointestinal cancer neoantigens by circulating PD-1+ lymphocytes. J Clin Invest. 2019.


Fostering The Design of Innovative Cell Therapies to Existing Immunotherapies for Non-Responders

Fostering The Design of Innovative Cell Therapies to Existing Immunotherapies for Non-Responders

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