Optimizing Adoptive Cell Therapy by Genetic Engineering of T cells for Improved Homing to Tumor Site

​PhD Student: Manja Idorn, MSc 

In recent years, the immunotherapy of cancer has emerged as a true contender for a successful and potentially curative treatment option within certain cancers. Adoptive cell therapy (ACT) represents a promising treatment modality for the treatment of disseminated cancer. The strategy of using in vitro expanded T cells from the patients' own biopsy material has led to clinical responses in up to 50% and potential cures in 20% of metastatic patients. However, obviously the remaining half of patients has no benefit from treatment yet suffers the harsh side effects. In its present form, ACT is rather crude, and thus improvements seem within reach.

Relying on the patient's own immune cells, recruitment of transferred lymphocytes to the tumor site is a prerequisite for successful ACT. Chemokine/receptor interaction plays an important role in T cell trafficking towards lymph nodes and inflamed tissues. However, many tumors express chemokines that divert homing of anti-tumor T cells and rather promotes homing of cells with suppressive action, thus promoting tumor progression and metastasis. To this end, quite few T cells eventually reach the tumor site upon ACT administration. By engineering T cells to express appropriate homing receptors we attempt to exploit the chemokine expression by tumors therapeutically. In the present pre-clinical study we will arm T cells with chemokine receptors CXCR2, CXCR4 and CCR2 by viral transduction. Through a series of in vitro validation and in vivo treatment studies, we aim at improving the homing of adoptively transferred T cells and augment the anti-tumor efficacy of ACT.