Exosome Therapeutics

Why Cancer Patients Need CAR-Exosome Therapeutics

  About Exosome Therapy

Why Cancer Patients need CAR-Exosome Therapeutics

Exosomes
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 to treat cancer?
How are exosomes used to treat cancer?

INOVIQ weaponzes 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 is a CAR?
What's a CAR and how will it help treat 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

CAR-Exosome Therapeutics In Vitro Data

 

  Exosome Therapeutics | Next-Gen Cell-Free Therapy

Next-gen cell-free therapy

  • The therapeutic effects of Cell Therapy are mediated by exosomes interacting with host cells
  • Cell-Free Therapies can be developed using exosomes isolated from allogenic MSC, T cells or NK cells grown in vitro
  • INOVIQ is developing weaponised exosomes engineered to target and kill solid tumours
  • CAR-exosomes inherit the targeting and cytotoxic properties of their parent cells to kill cancer
  • Next-gen “off-the shelf” cell-free therapy for solid tumours
  • Potential safety, efficacy and cost advantages over autologous CAR-T therapy

CAR = Chimeric Antigen Receptor; EV = Extracellular Vesicle or Exosome

  CAR-Exosomes | Allogenic EV-Based Therapy with Multiple Advantages
  • Improved efficacy in solid tumours due to ability to infiltrate TME based on nano-size (10-9)
  • Multiple doses and/or CAR-T follow-on or combination therapy
  • Continuous manufacturing from immortalised cells enabling off-the-shelf allogeneic therapy for any patient
  • Fast patient logistics and time-to-dose of ~1 week
  • Reduced manufacturing and supply chain costs
  • Lower treatment cost per patient benefiting patients & healthcare system
  • Improved safety profile due to reduced GvHD, CRS & secondary tumours as EVs don’t replicate in the body

Clinical Need and INOVIQ's CAR-EV Targets
  • Cancers for which there are no targeted therapies TNBC
  • Cancers where Cell Therapy has limited access glioblastoma

GvHD = graft versus host disease; CRS = cytokine release syndrome

  CAR-Exosomes | Mechanism of Action

CAR-exosomes mechanism of action

CAR-EVs inherit the targeting and cytoxic properties of their parent CAR-T or CAR-NK cells
  • CAR-EVs are produced by CAR-T/NK cells
  • CAR-EVs contains catalytic proteins, perforin and granzyme B
  • CAR-EVs interact and internalise into cancer cell
  • Catalytic proteins from CAR-EVs induce cancer cell death, apoptosis

CAR-EVs for drug delivery
  • RNA and small molecules for combination therapy
  CAR-Exosome Therapy | Development Path

 

CAR-Exosomes therapeutic development path to FIH studies