One of the most fascinating phenomena in cancer therapy is the so-called "abscopal effect." It is sometimes observed as a beneficial side effect of radiation therapy: when doctors irradiate one tumor site they occasionally also get an unexpected 'dividend' in the shrinkage or disappearance of tumors at non-irradiated sites. This phenomenon was first observed more than fifty years ago by Dr. R. H. Mole, of Britain's Medical Research Council. He coined the term 'abscopal effect' to describe it. (The word "abscopal" is derived from the Latin prefix "ab-" meaning "away from," and the Greek word "skopos," meaning "target.") CancerWeb has defined an abscopal effect as "a reaction produced following irradiation but occurring outside the zone of actual radiation absorption."

The abscopal effect is admittedly rare and in the past was considered somewhat controversial, since it seemed to fly in the face of common sense. How could radiation, by definition a local treatment, make distant, non-irradiated tumors disappear? However, like spontaneous remissions, which they resemble, abscopal effects have occurred often enough over the years to demonstrate that they are indeed real.

(To read what I last wrote about the abscopal effect, five years ago, please click or go to:
http://www.cancerdecisions.com/021403.html )

Harnessing the Abscopal Effect Experimentally

What if it were possible to give cancer patients a substance that would actually make the abscopal effect a routine part of treatment? This would change radiation from being a strictly local treatment (i.e., a treatment that only has an effect in the area to which it is directly applied) to a systemic treatment (i.e., a whole-body treatment in which any distant metastases are also beneficially affected even though they are not in the area directly targeted by the treatment).

It appears that scientists in Japan are well on the way to making that happen. A group of ten radiologists at the University of Tokyo, with senior researcher Professor S. Kanegesaki, have induced the abscopal effect in mice by first administering a biologically active protein or 'chemokine' called ECI301. ECI301 is an immune-modulating substance, an active variant of Macrophage Inflammatory Protein-1{alpha}. (Chemokines are complex molecules that activate and attract white blood cells. They are closely involved in inflammatory responses.) ECI stands for "Effector Cell Institute," the company that Dr. Kanegesaki founded after he retired from the University of Tokyo (http://www.effectorcell.co.jp/).

It is not exactly a new finding that immune stimulants can trigger the abscopal effect. Other researchers, such as the surgical pathologist, Sandra Demaria, MD, of New York University, have in the past noted that the effect is mediated by the immune system (Demaria 2004).

But in a Feb. 2008 article in Clinical Cancer Research, Prof. Kanegesaki and his Tokyo colleagues reported on their research, which was designed to show whether giving an intravenous dose of ECI301after local irradiation could prevent any remaining local, as well as distant, tumors from growing.

Colon cancers were implanted and grown in both flanks of laboratory animals. Tumors on the right side were irradiated. Then ECI301 was injected intravenously daily over a course of 3 to 5 consecutive days following local radiation treatment. Tumor volume was measured every 3 days. In about half of the treated mice the tumor was completely eradicated, not just at the site of irradiation but at distant sites as well.

ECI301 also worked in other experimental models of cancer besides colon cancer, including sarcomas and lung carcinoma. The researchers' most important finding was that tumor growth at non-irradiated sites was inhibited, which indicated that ECI301 may have enhanced the abscopal effect. The authors concluded that this study "may offer a new concept for cancer therapy, namely chemokine administration after local irradiation, leading to development of novel therapeutics for the treatment of advanced metastatic cancer" (Shiraishi 2008).

Harnessing the Abscopal Effect in Human Subjects

There has already been at least one attempt to harness the abscopal effect in human patients. This involved combining heat treatment, i.e., hyperthermia, with a type of viral therapy called H101. H101 is a genetically modified adenovirus that, according to the US National Cancer Institute, was approved in 2006 for cancer treatment by the Chinese equivalent of the FDA (Garber 2006).

This research involved five patients in Shanghai, China, each of whom had inoperable and metastatic tumors. Two patients had nasopharyngeal cancers, one had lung cancer, one had a sarcoma and one had bladder cancer. All of these patients had previously failed to respond to conventional chemotherapy and radiotherapy. The patients were given 60 minutes of hyperthermia at 42 degrees C (107.6 F) following intratumoral injections of H101 (i.e., the injections were given directly into the tumor). According to the sponsoring company, two of the patients "were cured with complete regressions of both injected and non-injected tumors and have survived for a long period up to date." (The article is only available in Chinese and the English-language abstract does not indicate how long they survived. It also does not state what kind of heat therapy was given. I have written to the company to find this information.)

The three remaining patients initially responded to this unusual combination but died from their disease at 29, 15 and 13 months, respectively. The authors, led by Hu Fang, MD, the president of the sponsoring company, concluded: "The abscopal anti-tumor effect could be induced by the combination of H101 local intratumoral injection with heating" (Hu 2006). In European CAM clinics hyperthermia is often combined with other immune-stimulating therapies, such as mistletoe extract injections.

It is exciting that scientists are once again actively pursuing this long dormant but promising field of research. I hope that someday immune modulating substances will routinely be administered along with radiation and other cytotoxic treatments in order to trigger the abscopal effect.

--Ralph W. Moss, Ph.D.