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Cytokines are a class of soluble molecular messengers that activate and transmit disease-fighting immune cascades in vivo in response to antigen-presenting cell stimulation
.
In cancer immunotherapy, exogenous cytokines can initiate immune system activation to optimize acquired antitumor immune responses
Many pro-inflammatory cytokines, including interleukin 2 (IL-2), IL7, IL12, IL15, and interferon-γ, have shown promising antitumor prospects in clinical trials
.
IL-2, in particular, has received much attention in cancer immunotherapy because it plays a key role in regulating immune cells such as T cells
Previously, the FDA has approved two types of recombinant IL-2 for the treatment of melanoma and kidney cancer by high-dose injection.
However, the half-life of IL-2 in the blood is only a few minutes, so high-dose infusion is required to bring significant effects.
.
Unfortunately, many cancer patients experience severe side effects when administered in such high doses, resulting in multiple organ damage, which has also hindered widespread use of this treatment
Recently, Rice University Omid Veiseh et al.
published a research paper entitled: Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors in Science Advances .
The study developed an in vivo "cellular drug factory" that uses microcapsules based on the natural material alginate to encapsulate engineered human retinal pigment epithelial (RPE) cells that stably express high levels of IL-2 and implant them near tumors.
In mouse models of advanced ovarian and colorectal cancer, tumors were nearly cleared in just 6 days
These findings demonstrate the safety and efficacy of the in vivo IL-2 cytokine factory in preclinical animal models and provide a basis for future human clinical trials
.
Human clinical trials will begin as soon as this fall, the research team said
A major challenge in the field of tumor immunotherapy is to increase tumor inflammation and antitumor immunity while avoiding the systemic side effects of cytokines and other pro-inflammatory drugs
.
Interleukin 2 (IL-2) is a cytokine that helps the immune system recognize and fight disease and is an FDA-approved cancer treatment
.
However, the half-life of IL-2 in the blood is only a few minutes, so large infusions are required to bring about a significant effect
In order to solve the above problems, the research team used the PiggyBac transposon system to stably express IL-2 at high levels in retinal pigment epithelial cells (RPE), and then encapsulated these engineered cells into alginate-based (natural polysaccharide extracted from seaweed) Carbohydrate, a natural polymer material, safe and non-toxic to human cells) in microcapsules
.
Human retinal pigment epithelial cells (RPE) were chosen because they are non-tumorigenic, suitable for genetic modification, and have proven safety in human trials
After encapsulation of these engineered cells into microcapsules, the cells continued to survive and continued to produce IL-2 stably for significantly longer periods of time in vivo than unencapsulated cells
.
The presence of the microcapsules protects these engineered cells from recognition and attack by the immune system
But this "cellular drug factory" elicits a stronger immune response than existing IL-2 treatments, because microcapsules encapsulating engineered cells deliver higher concentrations of the IL-2 protein directly to tumors
.
However, if this concentration of IL-2 is injected directly, it will be highly toxic.
The "cellular drug factory" method will only control the high concentration in the tumor site, and the concentration in other parts far from the tumor is much lower than the body can withstand during intravenous injection treatment.
concentration
.
Next, the research team carried out mouse model experiments.
The experimental results showed that this "cellular drug factory" could almost completely remove tumors in a mouse model of advanced ovarian cancer and a mouse model of colorectal cancer in just 6 days.
.
This is very exciting and provides a strong basis for clinical trials
.
Studies in non-human primate cynomolgus monkeys also show that this "cellular drug factory" is well tolerated and significantly activates the expansion and proliferation of cytotoxic T cells
.
The research team also said that placing such "cellular drug factories" next to tumors, and within the peritoneum surrounding these organs, could be used to treat cancers of the pancreas, liver, lung and other organs
.
If different cytokines are needed to treat a specific form of cancer, the microcapsules can be loaded with different engineered cells
.
Omid Veiseh, the corresponding author of the paper, said that the original intention of this research was to help patients defeat cancer as soon as possible, so ingredients that had previously been shown to be safe for use in the human body were selected, and the current series of experiments have proved the safety of this new type of therapy.
sex, with human clinical trials expected as early as this fall
.
Based on these findings, Omid Veiseh et al.
founded Avenge Bio, a company that, through its proprietary allogeneic LOCOcyte platform, precisely delivers cytokines or other immune-modulating molecules to locally modulate the immune system, thereby promoting a systemic anti-tumor immune response, Avoid the toxic effects of traditional immunotherapy and develop revolutionary treatments to eradicate intractable solid tumors
.
Avenge Bio's R&D pipeline
Avenge Bio's R&D pipeline Avenge Bio's R&D pipelineOriginal source:
Original source:AMANDA M.
NASH, et al.
Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors .
SCIENCE ADVANCES, 2 Mar 2022, Vol 8, Issue 9.