CRI Funded Scientists

Li Tang, PhD, CLIP Investigator

Ecole Polytechnique Federale de Lausanne (EPFL)

Area of Research: All Cancers

Adoptive T cell transfer (ACT) is a potent immunotherapy approach, in which a large number of tumor-killing T cells collected from a patient and expanded outside body are infused back to fight the cancer. ACT, specifically CAR T cell therapy, has shown astonishing efficacy against several cancers especially hematopoietic cancers such as leukemias. In CAR T cell therapy, T cells collected from a patient can be genetically modified to target a specific protein in tumor cells. However, such target protein may also exist in normal cells leading to “on target, off tumor” toxicity. This issue greatly limits the broad application of genetically modified ACT therapies to treat many solid tumors. Another method to prepare ACT T cells is to collect tumor-killing T cells directly from tumor biopsy or from blood without genetic modification. However, in most cases, an unsatisfactory number of T cells can be collected or the frequency of true tumor-killing T cells among the mixture is too low. Currently, there is no method available in the clinic to collect a large number of tumor-killing T cells with good purity from a reliable source.

Recently, Dr. Tang’s team found that treatment with the cytokine IL-10 could induce the significant enrichment of a specific subpopulation of T cells in the blood, called terminally differentiated CD8+ T cells. These T cells likely come from the tumor, and show the potent capacity to kill tumor cells and eventually completely clear the tumors in mouse models in his preliminary studies. Here, he proposes a new method of ACT, where tumor-bearing mice (mimicking patients) will be treated with IL-10 in order to enrich tumor-killing T cells in the blood. Next, these can be easily harvested with high frequency, expanded outside body, maintained with potent killing capacity, and finally infused into another tumor-bearing mouse as a new ACT immunotherapy. This groundbreaking strategy for ACT is distinct from all existing approaches and has advantages including great accessibility (in blood), high frequency of source T cells, and broad tumor antigen reactivity, showing extraordinary potential to enhance ACT immunotherapy in the clinic.

Projects and Grants

Cytokine-induced enrichment of peripheral tumor-reactive endogenous T cells for adoptive cell therapy

Ecole Polytechnique Federale de Lausanne (EPFL) | All Cancers | 2021

T lymphocyte engineering with Interleukin-2-silica nanocapsules for targeted cancer therapy

Massachusetts Institute of Technology | All Cancers | 2013 | Darrell J. Irvine, PhD

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