SCIENCE

Overcoming Immunosuppression

TriSalus is evaluating an immunotherapeutic agent to reprogram the tumor microenvironment (TME), overcome immunosuppression, activate the immune system, and enable immunotherapy success in liver and pancreatic tumors.

Modulatory Effects of TLR9 Agonists on Immune Cells

Interactive scientific illustration of the cell types with the tumor microenvironment where a reopened blood vessel allows a drug to diffuse into the tissue.
Myeloid-Derived Suppressor cells (MDSCs)

Immunosuppressive MDSCs are recruited to the tumor microenvironment. TLR9 agonists have been shown to reprogram and eliminate MDSCs, reducing their immunosuppressive effects.6
1 of 4
Natural Killer (NK) Cells

In tumors, NK cells are suppressed through various pathways but have shown reactivation upon TLR9 stimulation.6
2 of 4
Toll-Like Receptor 9 (TLR9) Agonists

TLR9 agonists have the potential to activate the immune system and promote anti-tumor activity through activation and modulation of immune cells. 1–5
3 of 4
Plasmacytoid Dendritic Cells (pDCs)

pDCs are suppressed in the tumor microenvironment (TME) but have shown reactivation through TLR9.6
4 of 4
Interactive scientific illustration of the cell types with the tumor microenvironment where a reopened blood vessel allows a drug to diffuse into the tissue.

Toll-Like Receptor 9 (TLR9) Agonists
TLR9 agonists have the potential to activate the immune system and promote anti-tumor activity through activation and modulation of immune cells. 1–5
1 of 4

Myeloid-Derived Suppressor cells (MDSCs)

Immunosuppressive MDSCs are recruited to the TME. TLR9 agonists have been shown to reprogram and eliminate MDSCs, reducing their immunosuppressive effects.6

2 of 4

Natural Killer (NK) Cells

In tumors, NK cells are suppressed through various pathways but have shown reactivation upon TLR9 stimulation.6

3 of 4

Plasmacytoid Dendritic Cells (pDCs)

pDCs are suppressed in the TME but have shown reactivation through TLR9.6

4 of 4

Immunosuppressive Myeloid-Derived Suppressor Cells (MDSCs)

Tumors within the liver and pancreas have specific immunosuppressive pathways that render therapies less effective.7 MDSCs accumulate within the liver and pancreas in the presence of cancer.6,8  

The immunosuppressive environment of these organs and the high level of MDSCs is believed to enable a tumor to evade the immune system9 and induce further resistance to immunotherapy approaches such as checkpoint inhibitors and CAR-T therapeutics.10,11

High levels of MDSCs have been observed in a number of cancers including primary liver, liver metastases, pancreatic cancer and melanoma.12,13

Barriers to Treatment in the Liver

Barriers to Treatment in the Pancreas

MDSC Reprogramming through Toll-like Receptor 9 (TLR9) Agonists

Stimulating TLR9 may promote anti-tumor activity by activating the immune system to help attack solid tumors and convert suppressive immune cells into more immunostimulatory subtypes.1,2

TLR9 agonists have been shown to convert immunosuppressive MDSCs into immunostimulatory macrophages, while also affecting other cell types.14,15 TriSalus is currently studying whether MDSC reprogramming can be used to enable immunotherapeutic treatments, including checkpoint inhibitors and cell therapy.

Myeloid cell depletion has been shown to sensitize tumors to systemic therapies, including chemotherapy, radiation, checkpoint blockade and chemoimmunotherapy.13,16

Candidate: Nelitolimod

Our investigational candidate nelitolimod is a TLR9 agonist aimed at reactivating the immune system.

The TriSalus™ Integrated Solution

We are currently conducting clinical studies to determine if our investigational TLR agonist, nelitolimod (also known as SD-101), has the potential to enhance the benefit of other immuno-oncology agents when infused by the Pressure-Enabled Drug Delivery™ (PEDD™) method.

Trisalus is studying the ability of nelitolimod to reprogram and deplete MDSCs and enable immunotherapeutic treatments for liver tumors, liver metastases and pancreatic tumors.

Overcoming Intratumoral Pressure

Our proprietary technology has been shown to overcome intratumoral pressure and reopen blood vessels.

TriSalus’ Platform Approach

TriSalus’ platform addresses two significant treatment barriers directly in the liver and pancreas. We believe that the administration of immune-enabling therapies (i.e., investigative nelitolimod) by the Pressure-Enabled Drug Delivery™ (PEDD™) method provides a means to treat these hard-to-reach tumors.

PLATFORM

CITATIONS

  1. Weihrauch MR, et al. Eur J Cancer. 2015;51(2):146-156.
  2. Melisi D, et al. Biomedicines. 2014;2(3):211-228.
  3. Adams S. T. Immunotherapy. 2009;1(6):949-964.
  4. Krieg AM. Oncogene. 2008;27(2):161-167.
  5. Karapetyan L, et al. Onco Targets Ther. 2020;13:10039-10060.
  6. Li X, et al. Nat Rev Cancer. 2021;21(9):541-557.
  7. Ma S, et al. Int J Biol Sci. 2019;15(12):2548-2560.
  8. Feig C, et al. Clin Cancer Res. 2012;18(16):4266-4276.
  9. Hegde S, et al. Immunity. 2021;54(5):875-884. 
  10. Thorn M, et al. Cancer Gene Ther. 2016;23(6):188-198.
  11. Burga RA, et al. Cancer Immunol Immunother. 2015;64(7):817-829. 
  12. Dysthe M, et al. Adv Exp Med Biol. 2020;1224:117-140. 
  13. De Cicco P, et al. Front Immunol. 2020;11:1680.
  14. Ghosh C, et al. J Immunother Cancer. 2021;9(Suppl 2):A637-A637.
  15. Ghosh CH, et al. AACR Annual Meeting. 2021.
  16. Tavazoie MF, et al. Cell. 2018;172(4):825-840.

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