{"id":18980,"date":"2020-01-28T12:00:00","date_gmt":"2020-01-28T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2020\/cancer-abscopal-effect-radiation-immunotherapy"},"modified":"2024-11-03T15:16:50","modified_gmt":"2024-11-03T15:16:50","slug":"off-target-investigating-the-abscopal-effect-as-a-treatment-for-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/off-target-investigating-the-abscopal-effect-as-a-treatment-for-cancer\/","title":{"rendered":"Off Target: Investigating the Abscopal Effect as a Treatment for Cancer"},"content":{"rendered":"

\n
\n
\n

Researchers are studying how treating a single tumor with radiation, or\u00a0radiation plus other treatments, may stimulate an immune response against tumors elsewhere in\u00a0the body\u2014a response known as the abscopal effect.<\/p>\n

Credit: Adapted from Clin Cancer Res September 2016. https:\/\/doi.org\/10.1186\/s13014-016-0693-8. CC BY 4.0.<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

The patient had run out of treatment options. Her cancer, a rare form of sarcoma<\/a>, had metastasized<\/a> and was no longer responding to therapies.<\/p>\n

As a next step, doctors at the Washington University School of Medicine in St. Louis began to treat her largest tumor with proton beam radiation. The goals were to slow the tumor\u2019s growth and keep the 67-year-old patient as comfortable as possible, recalled one of her doctors, Brian Baumann, M.D., a radiation oncologist<\/a>.\u00a0<\/p>\n

But after one course of proton radiation, the doctors noticed a surprising change in her scans: Not only had the irradiated tumor shrunk, but so had untreated tumors in other parts of her body.<\/p>\n

Over time, the tumors would continue to shrink, and eventually they went away.<\/p>\n

\u201cNearly 3 years later, she is alive and doing very well,\u201d said Dr. Baumann. His team reported recently that the patient appeared to have experienced a rare response to treatment known as the abscopal effect<\/a>.<\/p>\n

\u201cThe abscopal effect is a fascinating phenomenon,\u201d Dr. Baumann said, noting that it was first observed in experiments with mice in the early 1950s.<\/p>\n

The abscopal effect occurs when radiation treatment\u2014or another type of local therapy<\/a>\u2014not only shrinks the targeted tumor but also leads to the shrinkage of untreated tumors elsewhere in the body. Although the precise biological mechanisms responsible for the abscopal effect are still being investigated, the immune system<\/a> is thought to play an important role.\u00a0<\/p>\n

Waking the Immune System\u00a0<\/h2>\n

\u201cWhen you treat a single tumor in a patient who experiences the abscopal effect, you\u2019re waking up the immune system and enabling it to recognize other tumors in the body,\u201d said Billy W. Loo, Jr., M.D., Ph.D., a radiation oncologist at the Stanford Cancer Institute.\u00a0<\/p>\n

In response to radiation, tumor cells may release material that is recognized by the immune system as a threat, potentially leading to an immune response<\/a> throughout the body, explained Silvia Formenti, M.D., of Weill Cornell Medicine, whose research helped to establish a link between the abscopal effect and the immune system.<\/p>\n

\u201cThe irradiated tumor can become\u00a0a kind of vaccine<\/a>,\u201d added Dr. Formenti. This approach to treating cancer, which can be carried out in various ways, including with\u00a0radiation therapy, is called in situ<\/em> vaccination<\/a>.<\/p>\n

In recent years, the availability of new immunotherapy drugs and a greater understanding of how the immune system can work against cancer have contributed to a resurgence of interest in the abscopal effect among researchers, according to Dr. Loo.\u00a0<\/p>\n

The phrase \u201cabscopal effect\u201d was mentioned nearly 120 times in the PubMed database of scientific publications in 2019, up from just 4 mentions a decade ago.<\/p>\n

Much of this work has focused on understanding why the abscopal effect occurs. Researchers have also been testing combinations of treatments that may increase the likelihood that the abscopal effect will occur in patients with metastatic cancer.\u00a0<\/p>\n

A Historical Link to Radiation\u00a0<\/h2>\n

In the first description of the abscopal effect<\/a>, in 1953, a researcher named R. H. Mole showed that radiation could shrink a tumor on one side of a mouse and lead to the regression<\/a> of an untreated tumor on the other side of the animal.\u00a0<\/p>\n

To explain this treatment effect outside the field of radiation, Dr. Mole used the word abscopal, which is derived from the Latin for \u201caway from the target.\u201d<\/p>\n

For several decades after Dr. Mole\u2019s report, many radiation oncologists doubted the existence of the abscopal effect, as it was rarely observed. \u201cBecause the abscopal effect is unexpected and often dramatic, it became part of the lore of radiation oncology,\u201d said Dr. Loo.\u00a0<\/p>\n

But he and others point to growing evidence that the phenomenon is real and could potentially be made to occur more reliably.\u00a0<\/p>\n

Abscopal responses have been documented in various types of cancer, including melanoma, breast, lung, and liver cancers. In recent years, the effect also has been reported in patients with less common cancers, such as pleural mesothelioma<\/a> and cancer of the thymus<\/a>.<\/p>\n

Although the vast majority of radiation oncologists have never witnessed the abscopal effect in a patient, those who have say it is remarkable. \u201cAs a doctor, you are shocked when you see the abscopal effect in a patient,\u201d said Dr. Formenti. \u201cOnce you have seen it, you will remember it forever.\u201d<\/p>\n

Overcoming Barriers to the Immune Response\u00a0<\/h2>\n

The abscopal effect is uncommon in part because cancer cells have ways to prevent the immune system from finding and killing tumor cells.<\/p>\n

\u201cGiven how many barriers there are that prevent the immune system from detecting and killing established\u00a0tumors, radiation alone cannot be expected to elicit the abscopal effect,\u201d said Dr. Formenti. “Some of the established barriers to the recognition and rejection of cancer cells must also be removed.”<\/p>\n

For the abscopal effect to occur, \u201cyou have to overcome the biological mechanisms that are preventing an immune response from eliminating tumors,\u201d said Zachary Morris, M.D., Ph.D., of the University of Wisconsin, who has investigated treatments that could lead to the abscopal effect as part of the Cancer Moonshot\u2120<\/a>.\u00a0<\/p>\n

\n
\n
\n

PET\/CT scans of a dog with osteosarcoma taken over the course of\u00a048 hours after receiving molecular radiation therapy. The treatment delivers low doses of radiation to tumors throughout the body and may improve the immune response against these tumors.<\/p>\n

Credit: Printed with permission from Zachary Morris, University of Wisconsin<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Dr. Morris and his colleagues have been testing in mice an approach designed to restore the ability of the immune system to recognize and attack cancer cells once this ability has been lost.\u00a0<\/p>\n

In the approach, known as molecular radiation therapy<\/a>, low doses of radiation are delivered to all of the tumors in a mouse; at the tumors, the radiation temporarily eradicates immune cells called lymphocytes<\/a> that are preventing an immune response against cancer cells.\u00a0<\/p>\n

Dr. Morris pointed out that other lymphocytes in the body are unharmed by the radiation and would be available to mount an attack against tumors once the barriers preventing such attacks have been overcome.\u00a0<\/p>\n

\u201cWe plan to test the approach in dogs that develop cancer, which are a good model for humans because the cancers have occurred naturally,\u201d he said. \u00a0<\/p>\n

Combining Immunotherapy and Radiation\u00a0<\/h2>\n

Another strategy for triggering the abscopal effect is to combine radiation with drugs called immune checkpoint inhibitors<\/a>, which enhance the immune response to cancer.\u00a0<\/p>\n

There is growing evidence from clinical trials<\/a> that adding immune checkpoint inhibitors\u00a0to radiation boosts the chances of an abscopal response in patients<\/a>, compared with the use of radiation alone.<\/p>\n

The two approaches, noted Dr. Morris, may be complementary. Radiation may help the immune system to recognize tumor cells, while immune checkpoint inhibitors help it to respond more strongly.<\/p>\n

Although the combination therapy<\/a> may increase the likelihood of an abscopal response in some patients, the approach still \u201cdoes not reliably elicit the abscopal effect,\u201d said Dr. Loo, adding that there is \u201cconsiderable interest in learning how to optimize the strategy.\u201d<\/p>\n

Efforts are under way to improve the rates of abscopal responses among patients receiving both therapies, said Mansoor Ahmed, Ph.D., of NCI\u2019s Division of Cancer Treatment and Diagnosis<\/a>, who has led several scientific workshops on the abscopal effect.\u00a0<\/p>\n

\u201cBut the lack of data [from laboratory and animal studies<\/a>] about which doses and methods of delivering radiation are most likely to trigger an abscopal response in combination with immunotherapy has been a big challenge for the field,\u201d he continued.\u00a0<\/p>\n

Discovering Abscopal Responses\u00a0<\/h2>\n

Meanwhile, researchers continue to report unexpected abscopal responses associated with the use of various types of treatments that are delivered directly into tumors<\/a>.<\/p>\n

For example, researchers at Columbia University recently observed the abscopal effect during experiments with bacteria<\/a> that they engineered to deliver a type of immunotherapy drug known as a nanobody into individual mouse tumors. The drug targets a protein called CD47, which promotes the growth of some cancers.\u00a0<\/p>\n

When the bacteria were injected into a mouse tumor, they elicited an immune response that shrank the tumor. Some of the responding immune cells then migrated to other, untreated tumors and slowed their growth as well, the researchers found.\u00a0<\/p>\n

\u201cAs we expected, the tumor injected with bacteria disappeared within 10 days, but then we saw a very interesting abscopal effect in untreated tumors,\u201d said coauthor Sreyan Chowdhury, a Ph.D. candidate at Columbia University. \u201cThis was a surprise.\u201d\u00a0<\/p>\n

\u201cWe think the bacteria are serving a role that is similar to that of radiation in terms of stimulating an abscopal response,\u201d he added, noting that once the bacteria were injected into a tumor, they did not themselves spread to other tumors.\u00a0<\/p>\n

The approach could be a way to stimulate the immune system to find and attack tumors that are too small to be detected using imaging tools, added coauthor Tal Danino, Ph.D., a biomedical engineer at Columbia.<\/p>\n

Flu vaccines may be another treatment that could elicit the abscopal effect when injected into tumors, according to findings from a recent study of mice<\/a> that had melanoma tumors on opposite sides of their bodies.\u00a0<\/p>\n

\n
\n
\"A<\/div>
\n
\n

In experiments in mice, injecting the flu vaccine into a single tumor attracted immune cells that subsequently recognized and attacked cancer cells on the opposite side of the body.<\/p>\n

Credit: Printed with permission from Kajal Gupta and Andrew Zloza\/Rush University Medical Center<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Injecting a flu vaccine into one tumor not only reduced the growth of that tumor but also slowed the growth of the untreated tumor on the opposite side of the animal, researchers found.\u00a0<\/p>\n

\u201cWe saw the tumor growth slowing on both sides of the mouse almost simultaneously,\u201d said lead investigator Andrew Zloza, M.D., Ph.D., of Rush University Medical Center, whose laboratory has investigated how infectious agents, such as HIV, alter the body\u2019s response to cancer.\u00a0<\/p>\n

His team also injected flu vaccine into the tumors of mice with a form of breast cancer that spreads to the lungs, and the results were similar to those of the mice with melanoma.\u00a0<\/p>\n

In all of the mice, the flu vaccine drew certain immune cells that can recognize and attack cancer cells to the injected tumor. This changed the local tumor environment, setting the stage for the migration of some of these immune cells to other tumors, the researchers found. \u00a0<\/p>\n

\u201cThese immune cells can travel if there is a form of danger somewhere else,\u201d said Dr. Zloza. \u201cSo, they can find the other tumors in the body.\u201d More research, he noted, is needed to determine which types of immune cells were most important in the abscopal responses in the mice.<\/p>\n

To try to improve their results, the researchers treated mice with an immune checkpoint inhibitor as well as the flu vaccine\u2014and the strategy worked. The combination treatment yielded better responses in the mice than had occurred with the flu vaccine alone.\u00a0<\/p>\n

Flu vaccines approved by the Food and Drug Administration, which are inexpensive, readily available, and safe, could be tested in clinical trials as a potential treatment for cancer, noted Dr. Zloza, who is planning some of these trials.\u00a0<\/p>\n

\u201cIt\u2019s time for a clinical trial,\u201d he continued. \u201cWe need to see whether the flu vaccine can be repurposed as a cancer drug.\u201d \u00a0<\/p>\n

Exploring Proton Radiation\u00a0<\/h2>\n

The patient with sarcoma who was treated at Washington University School of Medicine and experienced the abscopal effect was among the first people to have such a response following treatment with proton radiation.<\/p>\n

Dr. Baumann pointed out that, when it comes to triggering abscopal responses, proton radiation may have certain advantages over more conventional types of radiation, which use high-energy radiation from x-rays, gamma rays, or neutrons.\u00a0<\/p>\n

A difference between these types of radiation is that gamma and x-ray beams do not stop as they pass through the body, whereas the depth of proton therapy beams can be controlled, potentially limiting the amount of\u00a0radiation that inadvertently reaches healthy tissues.\u00a0<\/p>\n

\u201cWith protons, you expose less of the body to radiation, which means you expose less of the blood and the circulating immune cells in the blood, which can kill tumor cells, to radiation,\u201d Dr. Baumann explained.\u00a0<\/p>\n

\u201cImmune cells are very sensitive to radiation,\u201d he continued. \u201cHigher exposure of immune cells to radiation can cause the immune cells to die, which may dampen the abscopal effect.\u201d<\/p>\n

More research, he added, is needed to explore the potential benefits of using proton radiation to treat other patients with the same type of sarcoma.\u00a0<\/p>\n

More Research and \u201cNew Rules\u201d\u00a0<\/h2>\n

Dr. Formenti noted that research is also needed to determine more effective and reproducible ways to use radiation to stimulate abscopal responses in patients with metastatic cancer.\u00a0<\/p>\n

Although many clinical trials are testing immunotherapy and radiation in patients with cancer, no large clinical trial has yet provided evidence to establish how the radiation should be delivered\u2014and in which doses\u2014to try to elicit the abscopal effect.\u00a0<\/p>\n

“We may have to change the way we deliver radiation to get the best results,\u201d she said. \u201cIt may not be as simple\u00a0as administering radiation the way it has generally been done.\u00a0<\/p>\n

\u201cWhen it comes to the abscopal responses,\u201d Dr. Formenti continued, \u201cthere may be some new rules we need to follow\u2014and we are still figuring out what those rules are.\u201d<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

January 28, 2020, by NCI Staff Researchers are studying how treating a single tumor with radiation, or\u00a0radiation plus other treatments, may stimulate an immune response against tumors elsewhere in\u00a0the body\u2014a response known as the abscopal effect. Credit: Adapted from Clin Cancer Res September 2016. https:\/\/doi.org\/10.1186\/s13014-016-0693-8. CC BY 4.0. The patient had run out of treatment […]<\/p>\n","protected":false},"author":2,"featured_media":18981,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-18980","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/18980","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=18980"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/18980\/revisions"}],"predecessor-version":[{"id":44346,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/18980\/revisions\/44346"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/18981"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=18980"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=18980"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=18980"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}