In vivo implantation of a "drug factory" releases IL-2 locally in tumors and clears tumors in mice w

In addition to conventional surgery, radiotherapy/chemotherapy, and targeted therapy, immunotherapy is now a novel cancer treatment strategy that works by having the body's immune system attack cancer cells.

As an important cytokine, interleukin-2 (IL-2) can effectively activate T cells and promote its growth, proliferation, and differentiation. In addition to IL-2, as many as dozens of interleukins have been identified up to now, which are named by numbers, such as IL-1, IL-12, and IL-38.

IL-2 has been used in cancer immunotherapy since 1992, when it was administered to patients by intravenous injection. Research based on IL-2 for the treatment of tumors started early and has shown some clinical efficacy. However, the half-life of IL-2 in human blood is only a few minutes, so large doses of IL-2 need to be administered to achieve the desired effect, which can lead to disorders of water and salt metabolism, abnormal function of multiple organs (kidney, liver, heart, lung, etc.), capillary leakage syndrome, and even cytokine storm, and these side effects have hindered the widespread use of IL-2 in immunotherapy.

Recently, a joint research group from Rice University and Baylor College of Medicine has developed an IL-2 "drug factory" that can be released locally in tumors, and by combining it with an immune checkpoint inhibitor drug can eradicate advanced mesothelioma in mice within a week, significantly improving the effectiveness of IL-2 treatment and minimizing side effects. They aim to perform clinical studies in the third quarter of this year and are aggressively promoting the translation of this research result into practical use.

The study is currently published in the journal Clinical Cancer Research under the title "Activation of adaptive and innate immune cells via localized Interleukin-2 cytokine factories eradicates mesothelioma tumors".

"Our creation of this drug factory offers a fresh way to distribute IL-2 that minimizes its side effects while boosting its anticancer benefits. In mice, it has been demonstrated that the drug factory significantly boosts the effectiveness of PD-1 immune checkpoint inhibitors, eradicates aggressive mesothelioma, and prevents recurrence. Positive results from this pilot research support the clinical assessment of an IL-2-based delivery system." According to Omid Veiseh, an assistant professor in Rice University's Department of Bioengineering and the paper's co-corresponding author.

The "drug factory" is an alginate microcapsule-based IL-2 drug delivery device. IL-2 has already received FDA approval for clinical use in the treatment of renal cell carcinoma and melanoma.

When implanted in the body, these "drug factory" produces high doses of IL-2 locally and continuously to activate immune cells to kill tumors. "IL-2 immunotherapy can kill tumors by activating immune cells, but its clinical utility is limited by pharmacokinetics, vascular leakage syndrome, and other life-threatening toxicities. Therefore, we developed this safe and clinically translatable local IL-2 delivery system to enhance immunotherapeutic efficacy while minimizing systemic IL-2 exposure." Omid Veiseh said.

In this study, Omid Veiseh's team used a mouse model of mesothelioma for their experiments. They implanted these "drug factories" through minimally invasive surgery next to the mesothelioma (within a thin layer of pleural tissue), used mass spectrometry flow cytometry to analyze changes in the immune cell population, and used complete blood counts and serum chemistry to evaluate the safety and efficacy of the drug delivery system, as well as to assess clinical translation. At the same time, Omid Veiseh's team has also combined the "drug factory" with an immune checkpoint inhibitor targeting PD-1 to treat mice.

The trial's findings revealed that while very little IL-2 entered the systemic circulation, which effectively prevented the side effects linked to systemic IL-2 exposure, the implantation of the "drug factory" led to a 150-fold increase in the concentration of IL-2 detected in the local area of the mice with mesothelioma. Furthermore, mesothelioma was eradicated in more than half of the mice given the "drug factory" implant alone, and in every mouse given the "drug factory" and PD-1 immune checkpoint inhibitor combination, mesothelioma was eradicated within a week without recurrence. All animals had their mesotheliomas eliminated within one week of the combination therapy with the implanted "drug factory" and PD-1 immune checkpoint inhibitor, with no recurrence.

In comparison to standard IL-2 therapies, this locally implanted "drug factory" generates high quantities of IL-2 close to the mesothelioma and triggers a more potent immune response. The "drug factory" "locks" high amounts of IL-2 just at the tumor site and at much lower levels elsewhere, without harming the organism, in contrast to direct injection of high doses of IL-2, which can have major harmful consequences on the organism.