Aurimune-TNF and T-Cells: A Surprising Result

T-Cells are all the rage these days, and with good reason. It’s hard to find an academic laboratory or big pharma company that isn’t throwing their lot behind a PDL-1 or CAR-T technology of one type or another. CytImmune is not heading down that path, but since immunotherapy in most of its current forms is focused on T-Cells, it’s important to set the record straight on our nanotechnology — more specifically, on how tumor necrosis factor alpha (TNF), when it is delivered on Aurimune nanomedicines, affects an important type of T cell known as a Treg (aka, Suppressor T cells).

Background Definitions

  • T cell, A type of white blood cell. T cells are part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer. Also called T lymphocyte and thymocyte.[Definition from NCI Dictionary]
  • Treg, Potent immunosuppressive cells of the immune system that promote progression of cancer through their ability to limit antitumor immunity and promote angiogenesis. [Definition from Facciabene et. al., 2012]

Most scientist, at least the ones who have an opinion on the subject, seem to believe that TNF increases the number and activity of Tregs inside solid tumors. If true, this would suggest that Aurimune nanomedicines should probably not be used with immunotherapies such as Keytruda or Opdivo, or in the future as a complementary treatment to CAR-T therapies. We don’t dispute the growing body of research, [example here], but since TNF is one of the most complicated molecules in the human body, we asked the NCI to take a look how the TNF on Aurimune affects the Treg populations in solid tumors. While they were at it, they also looked at a few other important T-Cell populations, T-helper cells and cytotoxic T cells. Here’s what they found.

The Short Answer

Tumor Necrosis Factor alpha delivered on Aurmimune nanomedicines does NOT increase the number of Tregs inside solid tumors.[We believe that is good news!]

Arimune nanomedicines may have a positive affect on CD4+ and CD8+ cells which are important participants in anti-cancer immunotherapies.

(see study details below)

First, a few notes about the studies:

  1. Tumor Necrosis Factor alpha was delivered using CYT-6091, a first generation Aurimune nanomedicine.
  2. Experiments were conducted at the Nanotechnology Characterization Laboratory (NCL), part of the NIH/NCI.
  3. CytImmune did not fund the experiments, but did provide guidance on how to deliver TNF using CYT-6091.
  4. Data were NOT published. Additional research was recommended by the group conducting the work, but this research was not approved for funding by the NCL.
  5. Two studies were performed including examining the affect of CYT-6091 on Tregs (CD4+, CD25+, FoxP3+), cytotoxic T cells (CD8+), and helper T cells (CD4+).

Study 1: KRAS/P53 Genetically Engineered Mouse Model

4 mice per group, animals injected with 5ug of TNF on day 1, sacrificed on day 3

  • CYT-6901 treatment showed an increase in CD4+ cells (p>.1) in tumors and CD8+ (p>.05) cells in peripheral blood compared to PBS.
  • No treatment related change was seen in the number of Tregs (CD4+, CD25+, FoxP3+) in either peripheral blood or tumor.

Study 2: KRAS/P53 Genetically Engineered Mouse Model

5 mice per group, 5ug of TNF delivered on days 1,3,5; mice sacrificed on day 8

Finding 1 of 3

  • CYT-6091 treatment results in an increase in CD4+ and CD8+ cells in tumor; this change is not statistically significant
  • There is no change in FoxP3+ cells

Treg Study 2 Finding 1 Data

Finding 2 of 3

  • CYT-6091 results in a decrease in CD3+CD4+ cells and an increase in CD3+CD8+ cells in both peripheral blood and in tumor; this change is statistically significant in tumor for CD8+ cells (p<0.05)

Treg Study 2 Finding 2 Data

Finding 3 of 3

  • CYT-6091 results in an increase in CD8+/CD4+ ratio among CD3+ T cells (p<0.05)
  • The increase in the ratio supports the conclusion that CYT-6091 stimulates cytotoxic T cells

Treg Study 2 Finding 3 Data

A Final Word

These findings are not definitive, but they are promising and suggestive. CytImmune continues to explore how TNF delivered on it’s Aurimune nanomedicines affects T cells and other other aspects of the tumor micro-environment.

As always, we are happy to answer questions related to this research, our technology, or the company. L eave a thought or ask a question in the comments section below, please the keep it civil and pardon us if it takes a few days to reply.

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