HBO shines light on novel immunotherapies
HBO’s Vice news program selected a few promising technologies from the immunotherapy pipeline to feature in its Killing Cancer episode. Vice’s heartrending human interest stories illustrated the potential of three different developmental drugs:
- An oncolytic measles virus battling myeloma.
- An oncolytic adenovirus fighting a brain tumor.
- An engineered human immunodeficiency virus knocking out childhood leukemia.
While this program has generated buzz around the hope for a cure, we were left to ponder: what exactly is the science behind the scenes? Let’s explore how oncolytic viruses battle cancer.
TERM OF THE WEEK: IMMUNOTHERAPY
Immunotherapy is a type of therapy that harnesses the power of a patient’s immune system to combat a disease.
ONCOLYTIC VIRUSES EXPLAINED
An oncolytic virus is a virus that infects cancer cells and multiplies inside of them, potentially rupturing and killing the individual cancer cells.
Oncolytic viruses are created in the lab by genetically modifying existing viruses in at least two ways:
- Making the virus safe by removing genes that cause the virus to make people sick.
- Engineering viral surface proteins so the virus recognizes and binds to the cell receptors of cancerous cells, disregarding the healthy, non-cancerous cells.
Additional modifications can be made to further equip an oncolytic virus, such as adding an immune stimulating gene to produce a granulocyte-macrophage colony-stimulating factor (GMCSF). GMCSF works to activate the patient’s own immune system and target the tumor.
Oncolytic viruses have yet to be approved by the FDA, but several are in clinical trials. Imanis Life Sciences’ (Rochester, MN) MV-NIS is an oncolytic measles virus in Phase I/II. DNAtrix’s (Houston, TX) DNX-2401 is an oncolytic adenovirus that just completed Phase I trials. Both were featured in the Vice episode.
The closest to market entry is Amgen’s (Thousand Oaks, CA) Talimogene laherparepvec (T-Vec), a modified herpes simplex 1 virus. T-Vec is engineered to target melanoma and express GMCSF to fight cancer cells (and not cause cold sores). With Phase III complete, an FDA decision is expected in the near future. Amgen is also aiming to expand the T-Vec market with an EMA submission in process.
Inside CAR-T Therapy
Scientists are engineering T-cells to recognize a specific tumor antigen, as seen in the case of young leukemia survivor Emily Whitehead.
The human immunodeficiency virus is engineered using the following process:
- T-cells are removed from the patient’s blood.
- HIV is prepared by researchers that strip their ability to cause illness; however, they retain their capacity to integrate into cells’ DNA. These viruses are then used to deliver genetic material to the patient’s T-cells in the lab.
- This results in a modified T-cell receptor, called a chimeric antigen receptor T-cell (CAR-T), that is able to recognize proteins on the surface of the patient’s tumor.
- The newly formed CAR-T cells are then multiplied in the lab.
- This group of CAR-T cells are infused back into the patient’s blood, where they ferret out and destroy tumor cells.
CAR-T therapy originated from research done by Dr. Carl June at the University of Pennsylvania (Philadelphia, PA), and was subsequently licensed and developed by Novartis. No CAR-T therapy has been approved by the FDA, but Novartis’ CTL019—used on Emily Whitehead—is in Phase II. The CAR-T market is swelling with other players such as Amgen, Kite (Santa Monica, California), Juno (Seattle, WA), Celgene (Summit, NJ) and Cellectis (Paris, France).
If engineered T-cells continue to live up to the hype, we can look forward to what some have termed a “living drug”—cancer fighting cells that will persist and multiply in a patient’s body until the tumor is destroyed.
COCKTAIL FODDER: NEW TECHNOLOGY, OLD OBSERVATION
While the idea of using viruses as a vector to fight cancer are gathering steam in the mainstream press, the technology has been around for over 100 years.
In 1904, a paper published in American Journal of Medical Science described the spontaneous regression of cervical cancer following a rabies vaccination. A few years later, this observation was followed by an account of the remission of lymphomas after measles virus infection.
The recent ability to engineer viruses to remove genes that create illness combined with the addition of specific tumor targeting genes make this century old speculation a likely reality.