Attacking Metastatic Breast Cancer

AUTHOR: David Oarr

I’ve had the pleasure of meeting and talking with many members of the metastatic breast cancer community over the past several months. In our discussions, I have mentioned that I believe CytImmune’s technology has the potential to help metastatic breast cancer patients live longer and higher quality lives.

As a follow-up to those conversations:

  • I would like to share an overview of CytImmune’s anti-tumor technology with a specific emphasis on metastatic breast cancer; and
  • I am asking for the support of the breast cancer community to get our technology out of the lab and into the hands of patients and doctors. At this point, support simply means helping us spread the word about our technology and signing our petition of patient support.

CytImmune’s Clinical Approach

The Clinical Problem:
Solid tumors, such as breast cancer tumors, have high internal fluid pressure (IFP).  High IFP pushes cancer therapies toward the periphery of the tumor and away from cancer cells growing in the tumor’s interior. This limits the effectiveness of radiation therapy, chemotherapy and even immunotherapy.  It’s a primary reason why tumors shrink after treatment, but then quickly grow back to their original size when treatment is stopped.

The Root of the Problem:
Breast cancer tumors require new blood vessels to grow.

These blood vessels are healthy but malformed.  In normal blood vessels, epithelial cells (see pink cells in diagram below) are tightly connected (see healthy blood vessel wall in diagram below). In tumor blood vessels, many blood vessel epithelial cells have gaps between them (see arrows in diagram below). These gaps allow fluid and small blood components to flow into tumors. The amount of material flowing in is greater than the amount of material flowing out. This creates a high fluid pressure environment inside all primary and metastatic breast cancer tumors.

Read More: Releasing Pressure in Tumors: What Do We Know So Far and Where Do We Go from Here? A Review

CytImmune’s Solution:
CytImmune has developed a nanomedicine, Aurimune™, that destroys solid tumor blood vessels in primary and secondary breast cancer tumors. Unlike therapies that slow new blood vessel growth over time (VEGF inhibitors like Avastin), our nanotechnology catastrophically collapses the tumor’s vasculature (blood vessel network) in a matter of hours or less.

Unlike most other systemically administered therapies, our nanotechnology targets tumors, but leaves healthy surrounding tissues and vital organs unharmed. Aurimune enters tumors through the gaps in tumor blood vessels and attacks the tumor micro-environment. Since non-tumor blood vessels lack gaps, Aurimune does not enter healthy patient tissues.

We have successfully completed a Phase I clinical trial, which demonstrated no significant adverse events and no dose limiting toxicity. We are raising funds to begin Phase II clinical trials.

Read More: Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicine

CytImmune’s Tumor Destroying Nanotechnology

CYT-6091, our first-generation nanomedicine, carries an immune/inflammatory molecule, Tumor Necrosis Factor alpha (TNF).  TNF is the most potent of a class of molecules called vascular disruption agents (VDAs). CYT-6091 is injected into a vein and travels safely through the body. When it reaches a primary or secondary tumor, CYT-6091 passes through the gaps between blood vessel epithelial cells. The TNF on CYT-6091 very quickly binds a receptor known as the  “death receptor”, which is present in a high concentration on all tumor blood vessel epithelial cells. Binding of TNF to the death receptor results in a rapid collapse and destruction of the blood vessels nourishing the tumor’s interior.

Read More: Exposing the tumor microenvironment: how gold nanoparticles enhance and refine drug delivery

After exposure to CYT-6091, many cancer cells in the tumor’s interior die, but that’s not the greatest benefit of CYT-6091. The altered tumor microenvironment with lower pressure provides anti-cancer agents access to the cancer cells they are designed to destroy. These anti-cancer agents may be administered independently, or they can be attached to CytImmune’s nanotechnology using our second-generation nanoparticles.

Attaching cancer-killing-agents to nanoparticles eliminates toxicity and dramatically increases anti-cancer effectiveness (Publication pending, 2017). We believe CYT-6091 and other Aurimune platform nanomedicines could be useful for many stages of breast cancer treatment, especially metastasized cancer.

Research Relevant to Breast Cancer Patients

When we tested CYT-6091 + fractionated radiation in an aggressive metastatic breast cancer mouse model, we observed a 5-fold delay in tumor growth.

We also observed that CYT-6091 destroyed peri necrotic blood vessels, and we demonstrated that CYT-6091 eliminates internal tumor pressure.

The clinically relevant benefit from eliminating the internal tumor pressure was delayed tumor growth and >50% of cancer cells killed (66% more tumor density reduction compared to radiation alone).

Read More: Combination of gold nanoparticle-conjugated TNF-α and radiation therapy results in a synergistic anti-tumor response in murine carcinoma models

In another set of experiments, we tested CYT-6091 + Paclitaxel (Taxol), a common breast cancer chemotherapy, in a genetically engineered mouse model (GEMM). We used a GEMM because the tumor blood vessel structure more closely approximates what we find in human solid tumors. [Feel free to ask questions about this. I am skipping over a lot of science!]

In these experiments, when CYT-6091 was given before chemotherapy, we observed a 6-fold increase in paclitaxel inside tumors.

The combination of a TNF + Chemotherapy has repeatedly demonstrated that, regardless of the chemotherapy used, pre-treatment with TNF results in more chemotherapy reaching the tumor and dramatically improved clinical outcomes.

Read More: Achieving a 95% response rate in solid tumors.

Moreover, when we attached paclitaxel to our nanotechnology and delivered it systemically to tumors, not only did more of the drug end up inside the tumor, but the side effects were nearly eliminated. And the clinical outcomes improved (Publication pending, 2017).

Our Phase 1 clinical trial (29 advanced stage IV cancer patients)  included a metastatic breast cancer patient. We biopsied one of the patient’s tumors and surrounding healthy tissue. We found our nanomedicine concentrated in cancerous tumor tissues, but not healthy tissues.

Read More: Phase I and Pharmacokinetic Studies of CYT-6091, a Novel PEGylated Colloidal Gold-rhTNF Nanomedicinef

A Summary for Breast Cancer Patients

CYT-6091 shows positive synergy with fractionated radiation, a common treatment for breast cancer patients. CYT-6091 also allows significantly more chemotherapy to reach cancer cells inside the tumor, dramatically improving the effectiveness of existing therapies. Based on the method of action for CYT-6019, we believe it could improve the effectiveness of any chemotherapy, radiotherapy and immunotherapy. We are working to validate a synergy with a common immunotherapy in preclinical experiments.

For those battling metastasized breast cancer, CYT-6091 reaches secondary tumors, which begin forming a protective micro-environment when they reach the size of a grain of sand (~1mm in diameter).

We are ready to begin Phase II trials for fractionated radiation + CYT-6091 and for chemotherapy + CYT-6091. We believe these have the potential to help metastatic breast cancer patients stay alive longer and maintain a higher quality of life.

*We  encourage patients and advocates to ask questions. You may enter questions in the comments section of this post, or reach out to us on Twitter, @CytImmune.

**Since CYT-6091 is a clinical stage product, we are unable to provide treatment outside of a clinical trial.

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