A new study from Aude Fahrer and her Australian colleagues deserves our attention, not so much that the suggested treatment must be adopted immediately but because we may wish to in the future and even if we don’t others will. This study reports on a series of trials conducted using a suspension of dead mycobacteria emulsified with mineral oil, which was injected directly into cancer tumors. A simple technique that costs next to nothing nevertheless seems to work.¹

This current report is the follow up to a March 2012 essay Fahrer wrote that was published in Immunology and Cell Biology.² Reading that paper is necessary to understand these current results. Fahrer proposed treating cancer with a combination of older pragmatic strategies that seemed to work. Recent advances in the understanding how dendritic cells function and how they trigger or silence T-cell responses led her to reconsider these therapies as now they can be explained. Her ideas drew directly from William Coley’s century-old attempts to fight cancer using bacterial toxins. Instead of Coley’s toxins, she proposed using the mixture of dead bacteria known as Complete Freund’s Adjuvant and injecting it directly into tumors rather than giving it by IV.

Cytotoxic T-cells can kill cancer cells directly. But as Fahrer explained, in order to do this, “…they must be primed (that is, initially activated and expanded) by dendritic cells. The function of dendritic cells is to continuously sample the proteins in a tissue (for example, those from cancerous cells or from infectious microbes) and then carry these proteins back to lymph nodes where they can be shown to T cells. Activated dendritic cells can prime T cells specific for the proteins they display. Once activated and expanded, cytotoxic T cells then return to the tissues to kill any other cell (in this case, cancer cells or infected cells), displaying the same protein….” In dendritic cells, the default setting is to turn off immune responses rather than to prime them. Most of the proteins dendritic cells move to the lymph nodes and present to T cells come from normal cells and it would be a problem if the dendritic cells were activated. Nonactivated dendritic cells turn off T cells preventing autoimmune disease against such normal proteins. The Toll-like receptors on the dendritic cells recognize microbial products like cell membrane materials or bacterial DNA or viral nucleic acids and see them as danger signals.³ Microbes or their remnants will activate dendritic cells getting them to prime an immune response.

Jules Freund first described his immune stimulating microbial cocktail in 1956, which was eventually named after him, Complete Freund’s Adjuvant (CFA).⁴ Immunologists have used this compound as a method to trigger immune responses in animal experiments for the half century since. CFA consists of heat-killed mycobacterium bacteria (usually M. tuberculosis) emulsified in mineral oil. Accustomed as we are to using high-tech nano-emulsions, it is refreshing to read that these emulsions are made just prior to injection by repeatedly drawing the mixture in and out of the dispensing vial into the syringe until the mixture thickens as it becomes emulsified. The injection creates a localized deposit of dead bacteria that slowly releases over a period of weeks to months. Immune cells are activated and drawn to the injection site in the tumor.

In her 2012 paper, Fahrer suggested that Complete Freund Adjuvant be emulsified with saline and then injected directly into tumors in order to activate the dendritic cells. These dendritic cells will have already sampled tumor proteins and priming them with the adjuvant would get them to present the tumor proteins to T cells and Fahrer predicted that this would trigger a potent anti-cancer T-cell response.

There is a parallel strategy already being used in cancer treatment known as ‘personalized dendritic cell vaccines.’ A patient’s dendritic cells are isolated and grown in vitro, loaded with cancer proteins, activated and then reinjected. This is a labor intensive and expensive procedure. “It takes about one to three months to make that personal vaccine. And it is expensive – it is probably going to cost about $100,000 for each person to make that vaccine….”⁵

In contrast activating dendritic cells in situ as Fahrer proposed is simple and cheap, about $20 for the ingredients and a single injection. We’ve talked for years about how spontaneous (think Saint Peregrine) infections or induced infections (think Coley’s toxins) can lead to tumor regression.⁶ Fahrer reminded her readers that “… our much ‘cleaner’ modern society, with aseptic surgery, and with the widespread use of antibiotics to treat bacterial infections—while evidently leading to a dramatic decrease in serious disease and death from bacterial diseases—has also led to a dramatic reduction in the rate of spontaneous cancer remissions.”

Fahrer’s proposed technique reminds us of protocols used by William Coley who initially injected a mixture of heat-killed Streptococcus pyogenes and Serratia marcescens into tumors. Coley’s success rates in treating cancer were so good, they are still hard to believe. Five-year survival rates for patients treated with Coley’s toxin were 43% for inoperable cancers (including carcinomas, melanomas and sarcomas) and 61% for operable cancers.⁷ The five-year survival rate for inoperable sarcomas was 52%, with 21% of patients remaining disease free for at least 20 years.⁸ Keep in mind that Coley’s procedure was intensive. Coley’s patients received daily injections or every other day for months on end. He initially injected the toxins directly into tumors in 1898, but by 1915 had shifted to intramuscular, and then intravenous injections.⁹

Fahrer proposed using CFA instead of Coley’s toxin. As mentioned, CFA is made from heat-killed mycobacteria. We are familiar with BCG as a cancer treatment, which is made from live Bacille Calmette-Guerin, another Mycobacterium bovis strain. For BCG to have an anticancer effect, it either needs intimate contact between the BCG and the tumor cells or the tumor and the BCG have to drain into the same regional lymph node drainage. Fahrer assumes that if live BCG is safe to use, dead CFA will be safer.

Another advantage of CFA over BCG is that the oil emulsion continues to act for weeks and often requires only a single injection; a single dose of CFA injected into a tumor should work as well as repeated doses of Coley’s toxins.

In August 2021, Fahrer’s group summarized their ongoing research in the Journal for Immunotherapy of Cancer. They have now tested CFA injections against three types of cancer in mice (breast, colorectal and mastocytoma), dogs (mastocytoma), and horses (melanoma).

Mice were injected with cell lines of rapidly growing cancers to produce tumors. CFA injections were helpful for the mice against mastocytoma and breast cancer but did not have a statistically significant effect against colorectal cancer. Mice given mastocytoma who were treated lived significantly longer than the control mice, 14 days vs. 10 days. Mice injected with breast cancer also survived significantly longer, 20 days vs. 17.5 days. In the colorectal cancer, the survival difference between CFA and placebo did not achieve significance, 14 vs. 13 days. Six of the 186 treated mice, about 3%, with mastocytoma had complete tumor regression and survived for up to two years without recurrence.

These mice studies were followed by a clinical trial treating naturally occurring mastocytoma in dogs. This cancer is common in dogs who will have a median survival of less than four months. Of 14 dogs treated with a single CFA injection, three showed complete regression of their tumors and two other dogs lived substantially longer than predicted.

A third animal trial involved gray horses. These horses are genetically highly susceptible to developing melanoma and more than 70% will get it. Eleven horses with melanoma were treated with CFA injections. Three of the horses showed clinical responses that included remission and reduction in mass size.

Fahrer and colleagues report that intratumor CFA injections have been tried on about a dozen human patients in cancer clinics in Switzerland and Australia after prior treatments had failed. Several of these patients experienced seemingly favorable responses; the most notable was a patient with metastatic renal cell cancer. Images of his retreating tumors are included in the current report.

All of the models used in these experiments have an inherent weakness. Fahrer clearly states that it takes a minimum of two to four weeks for the immune system to mount a significant response after CFA injections. The experimental animals, as well as the humans, in these trials, had such advanced terminal cancers that there was inadequate time to see an immune response take effect. Consider that the control mice with mastocytoma only survived ten days. Histology samples showed early signs of systemic immune responses against the cancer and these were positively associated with tumor regression.

It would make sense to consider CFA injections as a first line or early therapy rather than a last-ditch attempt after all other therapies have failed as was the case in the human subjects included. Multiple failed prior treatments likely left the immune response to adjuvant stimulation hampered. For CFA to work well, we would want a robust and healthy immune system. For example, with breast cancer, we might want to initiate CFA therapy immediately after an initial biopsy comes back positive.

CFA injections are probably outside the scope of most naturopathic doctors, though I admit to not being a legal expert on such matters. The human research is premature to encourage use. This probably won’t stop some patients or their providers from wanting to try this, even as a last-ditch attempt.

Fahrer’s proposed use of CFA is attractive in part because it is so congruent with naturopathic principles of treatment. The technique stimulates the inherent healing properties of the body, triggering the body’s immune system to act by employing a natural agent.

To use Fahrer’s words, this “could be a game changer. If this works well, it will be a new treatment option with far fewer side effects, which will be available for cancer patients….”

She goes on, describing CFA’s potential as a, “a game-changing low-cost and non-toxic treatment could offer people battling cancer a new alternative to chemotherapy.”¹⁰ “The best things about this new treatment is that it requires few doses, is simple to administer, and has low side effects,” but the real advantage and also its problem is cost.

As mentioned, the entire course of CFA treatment could cost as little as $20. In comparison, Keytruda (pembrolizumab), the popular immunotherapy drug, sells for about $10,000 per dose and is given at three- or six-week intervals for up to two years.

To paraphrase Willie Sutton, “go where the money is.” There is money to be made with the status quo and no profit in this new therapy, even if proven highly effective.

Yet not everyone in the world can afford modern cancer treatment. An estimated 1.3 billion people in the world live in severe poverty, defined as less than $2/day.¹¹

Years may be spent debating whether a $20 shot is more or less efficacious than $100,000 personalized treatments that might work better, but the poor of the world have no choice and CFA could become a common treatment based only on low cost and simplicity of administration. This alone is reason why we should be aware of Fahrer’s technique and her ongoing research.