Remove cancer cells in 6 days by Implanting a "cell drug factory" in the body

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Remove cancer cells in 6 days by Implanting a “cell drug factory” in the body

Remove cancer cells in 6 days by Implanting a “cell drug factory” in the body, and clinical trials will be carried out this year

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 about significant effects.

Unfortunately, many cancer patients experience severe side effects when administered in such high doses, resulting in multiple organ damage, which also hinders widespread use of this treatment.

Recently, Omid Veiseh et al. from Rice University 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.

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.

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 .

Remove cancer cells in 6 days by Implanting a "cell drug factory" in the body

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 a large dose infusion is required to bring about a significant effect. Unfortunately, many cancer patients experience severe side effects at such large doses, resulting in multiple organ damage.

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 (RPE) cells , 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.

Remove cancer cells in 6 days by Implanting a "cell drug factory" in the body

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.

Remove cancer cells in 6 days by Implanting a "cell drug factory" in the body

Omid Veiseh , the corresponding author of the paper, said that the original intention of this study was to help patients defeat cancer as soon as possible, so ingredients that had previously been shown to be safe for human use were selected, and the current series of experiments have proved the safety of this new type of therapy. sex, and human clinical trials are expected to begin as early as this fall .

Based on these findings, Omid Veiseh et al. founded Avenge Bio , which, through its proprietary allogeneic LOCOcyte platform, precisely delivers cytokines or other immune-modulating molecules to locally modulate the immune system, thereby promoting systemic anti-tumor immune responses, Avoid the toxic effects of traditional immunotherapy and develop revolutionary treatments to eradicate intractable solid tumors.