Skip to Content

A next-generation cell therapy platform meets an ideal target

IN BRIEF

The expected impact of our technology:

Potential in >50% of cancers

The breadth of HLA-G expression means that more patients could be eligible for CIR therapy.

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.

OUR TARGET

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)
HLA-G EXPRESSION

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.

HLA-G REACH

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

TumorsUS 2020 Incidence% HLA-G PositivePatient Size
AML19,94050% – 70%9,970 – 13,958
Breast279,10041% – 71%114,431 – 198,161
Lung228,82034% – 75%77,799 – 171,615
Colorectal147,95065% – 71%96,168 – 105,044
Renal (clear cell)73,75098%72,275
Endometrial65,62040% – 60%26,248 – 39,372
Pancreatic57,60036% – 64%20,736 – 38,864
HCC42,81043% – 67%18,408 – 28,682
Gastric27,60031% – 71%8,556 – 19,596
Ovarian21,75035% – 55%7,612 – 11,962
Incidence in the United States in 2020.

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.
OUR TECHNOLOGY

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

OUR SCOPE

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