Exosome Therapeutics

Why Cancer Patients need CAR-Exosome Therapeutics

What are Exosomes?
Exosomes are packages that cells use to communicate with each other. They function akin to a Parcel Post Service for the body. Cells load messages and cargo (including, RNA, DNA and proteins) into small packages (exosomes), stick on a delivery address label, add the sender’s information and then releases them into the blood. Upon reaching the recipient cell, the package is opened and the message is read and content utilized. The packaging protects the contents from damage during transit.
How are exosomes used in blood tests?

INOVIQ has developed ways to intercept exosomes during the delivery process (e.g. our NET technology). Similar to the Postal Inspection Service, our NET technology can identify and inspect specific packages to work out who sent them, where it’s going and what’s inside. For example, cancer cells release packages that are addressed to the body’s immune cells and say, “nothing to see here- all is fine”. This ensures that cancer cells evades detection.

INOVIQ’s TEXO-NET captures packages released by cancer cells into the blood, we can then find out where it came from (ovary, breast, prostate), where it’s going and what the message is. So, from a simple blood sample we can identify that there is a specific type cancer present. It is from this information that blood tests for detecting and monitoring cancer are developed. This also avoids taking an invasive tissue biopsy to get this information.

How are exosomes used to treat cancer?
INOVIQ weaponizes exosomes and returns them to the sender. The senders address label is added to exosomes that already contain their own cell-killing activity (cytotoxins). Exosomes can also be loaded with chemotherapy drugs or equipped with beacons that light up cancer cells allowing them to be seen and destroyed by the body’s immune system. One way to weaponize exosomes for therapeutic use is to use CARs.
What's a CAR and how will it help treat my cancer?
CAR stands for Chimeric Antigen Receptor and like the mythical creature that combines parts from various animals in to one, CARs are hybrid structures that combine a delivery address label (antigen-binding protein) and a key that turns on immune cells (a cell activating construct) into a single receptor that is placed on the surface of T-cells or Natural Killer cells. The “address label” directs the CAR-cells to where they are needed (e.g., to a breast cancer cell). Once they arrive, the activation key is turned and CAR-cell kills the cancer cells. This is referred to as CAR-cell therapy and has shown great promise in treating blood cancers (e.g. lymphoma).

 

What are the advantages for CAR-Exosomes?

INOVIQ is equipping exosomes with CARs, allowing the delivery of weaponized packages to specific cancer cells. The potential advantages of CAR exosome therapy over CAR cell therapy are many, including:

Safety

  • Treating cancers with CAR-exosomes avoids the use of Genetically Modified cells that have been associated with the development of secondary cancers. Recently, the FDA reported that in 19 cases of secondary T-cell malignancies following the use of CAR-T cells therapy. CAR-exosomes lack the capacity to replicate so cannot develop into cancers.
  • CAR-T cells are genetically modified immune cells and once injected into a patient can make and release damaging substances (cytokines), causing a life-threatening “cytokine storm”. CAR-exosomes only deliver their content to targeted cells and are not capable of making and releasing cytokines.

Effectiveness

  • To work effectively, CAR-T cells have to be in contact with cancer cells. This works well with blood cancers but it is less effective with sloid tumor, where CAR-cells must migrate through the dense matrix and mass of the tumor. CAR-exosomes are 1000-times smaller than CAR-cells. They can more readily penetrate solid tumors and even cross the blood-brain barrier to deliver their payload.

Commercial Viability

  • Manufacturing therapeutic doses of CAR-EV will be more cost-effective than for CAR-cells, as they can be produced continuously from immortalized cells.
  • Similarity, isolation, packaging, storage, stability and shipment of CAR-EVs is easier and cheaper, as CAR-EVs are not living cells.
  • Ultimately, CAR-EVs will be cheaper per dose – with benefit to the patients and the healthcare system.

CAR-Exosome Therapeutics In Vitro Data

  • INOVIQ is developing weaponised exosomes engineered to target and treat solid tumours.
  • Utilises proprietary EXO-ACE technology for large-scale isolation of exosomes for therapeutic use.
  • In vitro Proof-of Concept established in breast cancer cells showing >75% cancer cell death.
  • Further in vitro and in vivo studies (animal) planned in CY24 and CY25.
  • Potential advantages over autologous CAR-T/NK cell therapies (manufacturing, stability, safety1 and efficacy) for treatment of solid tumours.

 

1. US FDA investigating safety risks of CAR-T therapies using viral vectors (23/11/23) and requirement for a boxed warning on the risk of secondary T-cell malignancies (22/1/24)