A next-generation cell therapy platform meets an ideal target
The expected impact of our technology:
Enhanced specificity
Our CIR technology utilizes natural binding, refined by evolution, for optimal affinity.
Optimized signal transduction
Improved activation of our NK cells thanks to our proprietary CIR technology enabling longer survival of CIR-NK cells in vivo.
Exploited tumor vulnerability and improved durability of response
Our CIR therapy targets HLA-G expressed in both the tumor and in the TME.
Improved patient access
Our goal is to develop off-the-shelf products that offer efficacy, tolerability, cost-effectiveness, and ease of administration.
HLA-G, a powerful immune neutralizer
Human leukocyte antigen G (HLA-G) is a powerful immune checkpoint molecule—but it has been under-studied in immuno-oncology research. NKILT believes the time has come to tap its full potential as a target for cell therapy.
Understanding why begins with its role in pregnancy. In humans, HLA-G serves as an immune evasion mechanism, neutralizing all arms of the immune system to protect the fetus and allow development.
HLA-G is also found in, and protects, cancer cells.
- Obstructs cytotoxic T cells, along with natural killer (NK) cells and B cells
- Induces T-cell anergy, neutralizing their normal immune response
- Regulates myeloid cells
- Promotes T regulatory cells (Tregs)
An exquisitely tumor-specific antigen
HLA-G is expressed primarily in the placenta, with very limited expression in nonplacental normal tissue. When targeting HLA-G, we expect to see fewer on-target, off-tumor effects than with more broadly expressed targets, such as programmed cell death ligand 1 (PD-L1).
Healthy Tissue RNA Sequence: HLA-G
Source: The Human Protein Atlas.
Abbreviations: HLA-G, human leukocyte antigen G; PD-L1, programmed cell death ligand 1.
Upregulated in >50% of human cancers
In cancerous tissue, HLA-G is found more frequently. It is particularly activated in acute myeloid leukemia (AML), as well as in many solid tumors, representing more than half of all human cancers.
PD-L1 is expressed in approximately 15% of cancers.
HLA-G Incidence by Tumor Type
| Tumors | US 2020 Incidence | % HLA-G Positive | Patient Size |
|---|---|---|---|
| AML | 19,940 | 50% – 70% | 9,970 – 13,958 |
| Breast | 279,100 | 41% – 71% | 114,431 – 198,161 |
| Lung | 228,820 | 34% – 75% | 77,799 – 171,615 |
| Colorectal | 147,950 | 65% – 71% | 96,168 – 105,044 |
| Renal (clear cell) | 73,750 | 98% | 72,275 |
| Endometrial | 65,620 | 40% – 60% | 26,248 – 39,372 |
| Pancreatic | 57,600 | 36% – 64% | 20,736 – 38,864 |
| HCC | 42,810 | 43% – 67% | 18,408 – 28,682 |
| Gastric | 27,600 | 31% – 71% | 8,556 – 19,596 |
| Ovarian | 21,750 | 35% – 55% | 7,612 – 11,962 |
Sources: Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590 · Bukur J, Jasinski S, Seliger B. The role of classical and non-classical HLA class I antigens in human tumors. Semin Cancer Biol. 2012;22(4):350-358. doi:10.1016/j.semcancer.2012.03.003 · Carosella ED, Rouas-Freiss N, Tronik-Le Roux D, Moreau P, LeMaoult J. HLA-G: an immune checkpoint molecule. Adv Immunol. 2015;127:33-144. doi:10.1016/bs.ai.2015.04.001
Abbreviations: AML, acute myeloid leukemia; HCC, hepatocellular carcinoma; HLA-G, human leukocyte antigen G.
An ideal target for our CIR technology
With our novel and proprietary Chimeric ILT-Receptor (CIR) binding technology, NKILT has developed allogeneic, gene-modified CIR-NK cells to target the HLA-G pathway. We’ve devised a mechanism that takes advantage of characteristics of HLA-G to drive fit-for-purpose activation in NK cells.
By targeting the HLA-G pathway with CIR-NK cells, we propose to
Improve patient access
Cost-effective, scalable, off-the-shelf cell therapy
Provide broad coverage
NK cells’ innate anti-tumor toxicity can target the rare tumor cells that lack HLA-G expression
Offer efficacy and tolerability
Adoptive transfer of allogeneic NK cells has been validated for efficacy against AML cells and demonstrated a good tolerability profile
Ensure maximum specificity
Utilize natural receptors to mimic what nature does best
Reaching beyond the barrier
Factors within the tumor microenvironment (TME), such as hypoxia, stress hormones, or inflammation, could activate expression of HLA-G and other immunosuppressive cells. This can contribute to the strong barrier protecting the tumor from immune cells.
Our CIR technology could reach these immunosuppressive cells, including HLA-G, to break down the barrier.
The future of targeting NK-cell therapy against cancer
With potential in more than half of cancers, enhanced specificity, optimized signal transduction, and improved durability of response, our program stands to improve access for patients while providing efficacy, tolerability, and cost-effectiveness.
This is just the beginning. Learn more about how we’re working to bring exquisitely specific targeted cell therapy to patients with a broad array of cancers.
Find out more