Jeffrey C. Martin, Ph.D.
Founder at Oncoleader | Immuno-Oncology Biotech Analyst | Scientific Writer and Communications Specialist
Roanoke, Virginia, United States
Natural killer cell-based immunotherapy is taking the oncology world by storm. Who are the industry leaders?
If one were to embark on a journey into the vast expanse that is the NK cell immunotherapy landscape, you will soon encounter ImmunityBio.
ImmunityBio has a vast array of immunotherapy platforms and an extensive pipeline with over 6 active clinical trials at over 80 study locations, some in advanced stages of testing. They also give their platforms catchy acronymous names which, I have to admit, makes me think they'll perform better in the clinic (very scientific rationale).
Here, I lay out their various cancer therapy platforms and give a brief overview of the innovative mechanisms of action. Check out the accompanying graphic for clinical trial status.
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ImmunityBio's Oncology Platforms
1. Their leading compound, Anktiva (N803), is an IL-15 "superkine": a fusion between a mutated version of the cytokine IL-15 (IL-15 N72D --> this mutant has higher affinity for IL-15 receptors on NK and T cells) and the α-chain of the IL-15 receptor. Fusing IL-15 to the α receptor allows the compound to be administered systemically where it can interact with cytotoxic NK and T cells, acting as a potent anti-tumor stimulant.
2. Aldoxorubicin is an albumin-bound form of the chemotherapeutic agent Doxorubicin. The albumin keeps the drug in an inactive state and is tethered via a pH-sensitive linker. This link is cleaved within acidic (low pH) environments, for example, the tumor microenvironment. This increases intratumoral concentration and reduces off-target toxicities.
3. Their t-haNK cells ("tumor-targeting, high-affinity CD16-expressing NK" cells) is their newest and most promising platform. These are natural killer cells that express a high-affinity CD16 molecule which allows the cells to participate in antibody-dependent cellular cytotoxicity (ADCC). They also express a chimeric antigen receptor (CAR) which mediates tumor antigen-directed targeting. These two receptors provide the NK cells with TWO stimulatory signals against tumor cells. ImmunityBio currently has two variants of their t-hANK cells - one that expresses a PD-L1-targeting CAR and another expressing a CD19-targeting CAR.
4. Finally, their memory-cytokine-enhanced NK (M-ceNK) cells are NK cells that are immunologically enhanced in vitro with three cytokines: i) IL-15, ii) IL-12, and iii) IL-18. Treatment with these cytokines grants these NK cells LONG-LASTING MEMORY functions and enhances their anti-tumor efficacy. M-ceNK cells have displayed anti-tumor activity MONTHS after initial infusion - this is very long time for NK cells.
Be sure to follow me for more immunotherapy summaries like this. I plan to be doing this kind of thing very often, focusing on companies that are developing NK-based, innate cell engager, and cytokine-based immunotherapy platforms.
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