The counterattack of exosomes from "cell garbage" to "seed rookie"

Recently, a company focusing on exosome platform technology and innovative drug research and development - Suzhou VesiCURE Technology Co.

Discussions and preparations started last summer, and operations were officially started in October this year.

Misunderstood cellular "garbage"

In 1983, the research group of Rose M.

"Golden Track" Carrying Hope

As a result, major well-known pharmaceutical companies have begun to lay out the industrialized medicinal research of exosomes

In China, the popularity of exosome research is also rising.

At present, the research and development of exosomes in academia and industry mainly focus on four aspects: exosomes as markers for early diagnosis of diseases, exosomes themselves as disease treatment drugs, inhibition of exosomes, and as drug delivery vehicles.

"Exosomes as diagnostic markers for cancer"

Since exosomes can be detected in bodily fluids such as blood, urine, saliva, and cerebrospinal fluid, they are considered non-invasive or minimally invasive biomarkers for disease diagnosis, with the potential to detect many pathological conditions including cancer potential

"Exosomes as Cancer Immunotherapy"

The success of immune checkpoint therapy in several cancer types has raised interest in further exploration of immune dysregulation in tumors, including exosomal tumor immunotherapy, which could lead to anticancer vaccines

"Inhibition of Exosomes"

Elevated levels of exosomes are often associated with the progression of different types of cancer, and some researchers hope that by reducing tumor exosomes to normal levels, poor prognosis can be prevented

"Exosomes as a Drug Delivery System"

Traditional drug delivery methods include synthetic lipid nanoparticles and viral vectors, but both approaches have limitations, including the area of ​​the body they can reach, the number of cells in tissues they can reach, and their ability to avoid triggering a harmful immune response

Because they are composed of human proteins and lipids, exosomes are inherently non-immunogenic, non-toxic and capable of crossing biological barriers (such as BBB), which have unique advantages as drug delivery vehicles, and are currently the most concerned The direction of exosome application

Chinese and foreign pharmaceutical companies compete on the same stage

2015 is the first year of exosome industrialization

In the same year, Flagship Pioneering, a biomedical venture capital institution, incubated Codiak BioSciences, focusing on drug development with exosomes as delivery vehicles

According to incomplete statistics, there are currently nearly 50 companies in the world that are actively deploying the exosome track.

COVID-19 has accelerated the industrial development of small nucleic acid and protein drugs, and many pharmaceutical companies around the world have reached a number of cooperation on the development of exosome delivery technology drugs

In June 2020, Sarepta Therapeutics entered into a collaboration agreement with Codiak BioSciences to study exosome delivery vehicles and payloads for drugs for neuromuscular indications

The proprietary BioDrone™ technology platform of MDimune of South Korea is an exosome-based drug delivery platform, which can obtain exosomes from a variety of different cell sources by extrusion method to achieve personalized targeted delivery of biomolecules.
Minimize molecular drug dosage and side effects, and further improve drug efficacy
.
In May 2021, Reyon Pharmaceuticals and MDimune entered into an agreement to jointly develop the track
.
NeoCura, a Chinese company, is a technology innovation company that researches RNA precision medicine based on artificial intelligence
.
In October 2021, it also reached a cooperation agreement with MDimune to jointly develop mRNA therapy based on exosome delivery of cancer vaccines
.

In addition, Chinese pharmaceutical companies such as Enzekangtai, Aisai Bio, Berger Bio, and Visierkang have also deployed in the exosome therapeutic drug track
.
Among them, Enze Kangtai has developed pipelines in the fields of rare diseases and tumor immunity
.
Use exosome-based protein replacement therapy to supplement specific proteins missing from cells in rare disease patients
.
By activating the immune signals of tumor patients' immune cells by exosomes, combined with PD-1/L1 monoclonal antibody drugs, the normal anti-tumor immune response of cancer patients can be restored
.
Visierkang takes the engineering exosome drug delivery platform modEXO as a breakthrough point, researches innovative drugs for tumors and liver diseases, and simultaneously develops the application of exosomes in respiratory, neurological, digestive, immune diseases and other fields
.

Clinical trial data is expected to cross the line positively”

In terms of specific research results, many exosome drugs studied by Codiak BioSciences have entered the clinical trial stage
.
Among them, exoSTING consists of exosomes that have been engineered to carry a small molecule STING agonist in the cavity, and the other exoIL-12 is an exosome that has been engineered to express pro-inflammatory IL-12 on its surface
.
In November this year, Codiak BioSciences announced that exoSTING has obtained preliminary positive data in the first phase 1/2 clinical trial of monotherapy in solid tumors: the drug can activate the STING signaling pathway in a local dose-dependent manner in the tumor, and further activate the immune response
.
Exosome drug exoIL-12 enhances IL-12 dose control while limiting its associated toxicity, Codiak Bio Sciences develops exoIL-12 for the treatment of cutaneous T-cell lymphoma, melanoma, Merkel cell carcinoma , Kaposi's sarcoma, glioblastoma multiforme, and triple-negative breast cancer, and a Phase 1 clinical trial has been conducted in patients with early-stage cutaneous T-cell lymphoma
.

Kalluri, co-founder of Codiak BioSciences, is developing siRNA-containing exosomes, RASG12D, for pancreatic cancer
.
It is reported that this is a targeted exosome therapy for RAS
.
Because RAS is one of the most commonly altered proteins in tumors
.
While current drug research targeting RAS has focused on small molecules of the oncogene G12C mutant, Kalluri has set his sights on the G12D mutant, a target site commonly seen in pancreatic cancer
.
Kalluri's RASG12D, which improved survival in models of pancreatic cancer, is now in Phase 1 clinical trials
.

It can be said that the exosome industry is showing a situation in which a hundred schools of thought contend and a hundred schools of thought contend for success.
It is still unknown who will stand out from the competition and cross the line first, but judging from the current research progress, this day is not far away
.
It is expected that in the future, exosomes, as a new delivery carrier and treatment method, will bring new paths for the development of vaccines and nucleic acid drugs, relieve pain and bring new vitality to patients with various cancers and rare diseases
.

References:

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[2] https:// https://baijiahao.
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[4] https:// https://