Cancer Ablation

Image-Guided Cancer Ablation

Image-guided cancer ablation involves the placement of needles into a tumor, then the tumor is destroyed using extreme heat (microwave or radiofrequency) or extreme cold (cryoablation) to directly kill the cancer. Initially developed in the 1990’s for liver cancer, today it is used in many cancer types and locations.

Research work by Den Brok (1) has demonstrated the underlying immune response of ablation. Ablation of cancer can function like a vaccination against the tumor, generating an immune response.

In typical vaccinations, the disease-causing agent is killed or weakened and injected into the body. Ablation results in the killing of tumor within the body, leaving pieces of cancer that can potentially be recognized by the immune system.

Studies have demonstrated that ablation has the potential to be more effective, than surgery for the treatment of local tumors. However, for most cancer patients, it is the spread of the tumor from the original location “metastases” that ultimately results in their death. For metastatic disease, systemic therapies, such as chemotherapy, have been the only option for treatment, and overall not as effective as desired.

Now it appears that the immune response produced by ablation, combined with intra-tumoral injection of immunotherapy agents, such as Yervoy, Opdivo and Keytruda, can create a highly effective anti-cancer immune response with eradication of cancer, even beyond the directly treated site.

Immunotherapy

Immunotherapy

In recent years there has been a resurgence of immunotherapy, thanks to a deeper understanding of the immune system. It is now recognized that the cancer can actually use the immune system to protect itself, thus shutting off the part of the immune system that would attack it. The identification of receptors used by the cancer cell to shut off the immune system, has allowed the development of effective immune therapies. When these receptors are blocked, the immune system has the opportunity to recognize the cancer and learn to attack it. The main drugs currently available are CTLA-4 inhibitor (Yervoy) and PD-1 inhibitors (Opdivo and Keytruda). The FDA has approved these therapies for Melanoma. Opdivo is also approved for non-small cell lung cancer.

INJECTION OF IMMUNOTHERAPY

To date, Yervoy, Opdivo and Keytruda have been approved for systemic therapy. This means these medications are given intravenous, thus treating the entire body.

However, research by Marabelle (2) and also Den Brok (3) have shown that treatment directly into the tumor is far more effective that systemic treatment of the whole body. It has been shown that immune dysfunction occurs in the “microenvironment” of the tumor. This work supports that there should be a new paradigm shift in cancer immunotherapy, targeting directly to the tumor. This is far more logical and further supports the idea of “Precision Medicine.”

The problem with most typical cancer therapies is that they “poison” or treats the whole body and they do nothing to teach the body how to fight the cancer in the future. The current treatments are often ineffective in ridding the body of all the cancer. Once the medicines are stopped, or resistance develops, the cancer again progresses. The “key” to cancer therapy is to teach the immune system how to fight the cancer.

The immune system learns and has memory. This is why you can be vaccinated against something now, and fight the disease off when you are exposed to it many years, even decades later. This is how the combination of immunotherapy and ablation works. The ablation kills the tumor, leaving dead pieces and releasing substances to stimulate the immune response. The immunotherapy such as Yervoy, Opdivo and Keytruda, takes the brakes off the immune system, allowing it to attack the dead tumor. This trains the immune system to attack the cancer in other locations as well.

Now it appears that the immune response produced by ablation, combined with intra-tumoral injection of immunotherapy agents, such as Yervoy, Opdivo and Keytruda, can create a highly effective anti-cancer immune response with eradication of cancer, even beyond the directly treated site.

Immunotherapy combined with Image Guided Cancer Ablation (AblationVax™)

The combination of immunotherapy with image guided cancer ablation creates a much stronger anti-cancer immune response than either of the therapies alone. The results from just immunotherapy by itself, has created significant media attention, as one of the “greatest advancements” in cancer treatment. In published animal studies, further supported in our early human work, by adding ablation with immunotherapy, we expect to see a 3-5x greater increase in overall long-term survival than immunotherapy alone.

As, for the underlying mechanisms, it is well established the improved anti-cancer immune response by the immune checkpoint inhibitors, such as anti-CTLA 4 (Yervoy) and anti-PD-1 (Opdivo and Keytruda). However, less known is how ablation of cancer stimulates the immune response as well. Ablation results in tumor destruction inside the body. This results in the release of antigens. Antigens are the pieces of tumor that the immune system can recognize and learn to attack other tumor that contains those similar pieces. In addition, the ablation process results in the local release of other substances, which further enhance the immune response. These substances are known as Pathogen Activated Molecular Patterns (PAMPS) and Danger Activated Molecular Patterns (DAMPS). It is these substances that further set off an alarm to fight against the cancer. When you combine the release of “DAMPS”, “PAMPS” and tumor antigens, along with the immune checkpoint inhibitors (Anti-CTLA 4 and PD-1), you create a near perfect mix of immune stimulation, resulting in a much more powerful anti-cancer immune response. This combination results in stimulating the immune system against the cancer throughout the whole body, in a way that has never been achieved before.

Now it appears that the immune response produced by ablation, combined with intra-tumoral injection of immunotherapy agents, such as Yervoy, Opdivo and Keytruda, can create a highly effective anti-cancer immune response with eradication of cancer, even beyond the directly treated site.

Breast Cancer Cryoablation

THE NEW FUTURE OF BREAST CANCER TREATMENT

First there was mastectomy, then lumpectomy, now image guided cryoablation. Though still not accepted as a standard treatment option, image guided breast cryoablation has many advantages. Not only is the cosmetic result better, but also the immune stimulation may reduce chances of metastatic disease in the future. Dr. Williams performed one of the first breast ablations by RFA in 2003, then by cryoablation in 2004. The initial patients were ones who were either refusing surgery or their disease was very advanced, but they still had an untreated tumor in their breast. One of the first patients treated had stage 4 disease, and she lived 11 years after treatment, according to Dr. Williams.

Advantages of Breast Cryoablation:

  • Breast Cryoablation is less invasive
  • Breast Cryoablation has improved cosmetic results
  • Breast Cryoablation can be used to stimulate a “whole body” anti-cancer immune response

Intra-arterial Infusion of Immunotherapy

INTRA-ARTERIAL INFUSION OF IMMUNOTHERAPY

In certain tumors, especially in the liver, the arterial supply allows a direct access where larger amounts of medication can be applied directly to the tumor, with a lower dose to the patient. We use the immune checkpoint inhibitors (Yervoy, Opdivo and Keytruda) mixed with an oil-based substance for slow release, infused directly into the artery of a tumor. This is similar to chemoembolization, but instead of chemotherapy, we use immunotherapy.