Intra-tumoral delivery of IL-27 using adeno-associated virus stimulates anti-tumor immunity

Aiyan Hu (China)
Xue-Feng Bai, faculty mentor

Background

• Hometown: Hunan, China
• Degrees received: Medical Degree in clinical medicine, Soochow University, China

What is the issue or problem addresses in your research?

A potential caveat of systemic delivery of IL-27 using rAAV to inhibit tumors is that there is no practical method to terminate IL-27 production when its biological activity is no longer needed. Therefore, we tested if directly injecting AAV-IL-27 into tumors could lead to similar anti-tumor effect yet avoiding uncontrolled IL-27 production. Moreover, we also look into the mechanism of how IL-27 induces chemokines and what kind of role they play in the anti-tumor of IL-27.

What methodology did you use in your research?

After intra-tumor injection of AAV-IL-27, we measured tumor size of mice and two weeks later, we sacrificed mice and analyzed the tumor and spleen tissue. We used multi-color flow cytometer to analyze cell subsets and their function changes in the tumor microenvironment and peripheral lymphoid organs. ELISA test was used to measure the concentration of IL-27 in vivo and in vitro. Beside, STAT1, STAT3, CCL5, and IL-27R gene knock out mice were used to study the signal pathway.

What are the purpose/rationale and implications of your research?

Intra-tumoral delivery of AAV-IL-27 is a feasible approach for enhancing anti-tumor immunity, which can be used alone or in combination with anti-PD-1 antibody for the treatment of cancer. Moreover, since the expression of CCL5 induced by IL-27 promotes tumor progression, IL-27 gene therapy combined with CCL5 blockade would also further improve the therapeutic efficacy.