{"id":13752,"date":"2019-10-15T12:00:00","date_gmt":"2019-10-15T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2019\/oncolytic-virus-improves-immune-cell-metabolism"},"modified":"2024-11-03T15:17:07","modified_gmt":"2024-11-03T15:17:07","slug":"dual-function-virus-engineered-to-kill-tumor-cells-and-support-immune-cells","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/dual-function-virus-engineered-to-kill-tumor-cells-and-support-immune-cells\/","title":{"rendered":"Dual-Function Virus Engineered to Kill Tumor Cells and Support Immune Cells"},"content":{"rendered":"

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A cell infected by a vaccinia virus. Some of the oncolytic viruses being studied are engineered vaccinia viruses.<\/p>\n

Credit: J Cell Biol. April 2005. CC BY 4.0<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Viruses engineered to kill cancer cells are already used to treat one form of skin cancer and are being widely tested as treatments for other cancers.<\/p>\n

A new study suggests that such viruses, known as oncolytic<\/a> viruses, can be further enhanced to improve the body\u2019s immune response<\/a> against tumors. This new type of oncolytic virus, the researchers found, can simultaneously kill cancer cells and provide immune cells drawn into tumors with a hormone they need to perform their own cell-killing functions<\/a>.<\/p>\n

In mice with melanoma tumors, the dual-function virus was far more effective at shrinking and eliminating tumors than a standard oncolytic virus.<\/p>\n

The study\u2019s findings were published September 17 in Immunity<\/em>.<\/p>\n

\u201cThe new thing here is that this virus has been engineered to relieve immunosuppression<\/a>\u201d in addition to killing tumor cells outright, explained Phillip Daschner, program director in NCI\u2019s Division of Cancer Biology<\/a>, who was not involved with the study. \u201cIt\u2019s an idea that may be quickly translated to use in patients.\u201d<\/p>\n

Shut Down by a Toxic Environment<\/h2>\n

Oncolytic viruses kill individual cancer cells, but studies also suggest that they can boost the immune system\u2019s ability to recognize and kill a tumor.<\/p>\n

The viruses enter tumor cells specifically and replicate, eventually breaking the cells apart. When this rupture happens, tumor cell proteins that can be recognized by the immune system\u2014called tumor antigens<\/a>\u2014get released into the bloodstream. This process can draw T cells into a tumor to start killing cancer cells, and potentially may even trigger them to recognize metastatic cancer elsewhere in the body.<\/p>\n

But getting T cells to reach and enter a tumor is only part of the challenge, explained Greg Delgoffe, Ph.D., of the University of Pittsburgh Medical Center, who led the new study. \u201cThe tumor environment by its own nature is toxic,\u201d he said. \u201cWhen T cells get in, they experience a harsh, low-oxygen, desert-like landscape.\u201d This environment can render immune cells unable to function.\u00a0<\/p>\n

Dr. Delgoffe\u2019s lab had been testing an oncolytic virus (an engineered version of the Vaccinia<\/em> virus) to better understand how interactions between cancer and immune cells change after viral infection of a tumor. They found that, when injected into tumors in mice, their virus was able to induce substantial numbers of T cells to enter tumors.\u00a0<\/p>\n

The newly arrived T cells appeared to be healthy and vigorous, the researchers found. But T cells\u2019 ability to kill can fade, transforming them from powerful destroyers to depleted bystanders with limited capacity to harm cancer cells\u2014a phenomenon often referred to as exhaustion.<\/p>\n

The T cells that Dr. Delgoffe and his team initially found in the tumors were not exhausted, suggesting that they were newly arrived in the tumors. However, additional tests showed that these newly arrived T cells quickly developed metabolic<\/a> problems after entering the tumor.<\/p>\n

People often refer to immunotherapies as \u201caccelerators,\u201d or agents that \u201ctake the brakes off\u201d the immune system, Dr. Delgolffe said. \u201cBut accelerators and brakes don\u2019t matter if there isn\u2019t any gas in the tank.\u201d\u00a0<\/p>\n

\u201cThe virus on its own did a really good job of getting the immune cells activated,\u201d he said. So the research team wanted to enhance the virus, he continued, so that it would secrete something into the local environment to provide the gas for the T cells.<\/p>\n

Supporting T Cells<\/h2>\n

The team quickly zeroed in on a hormone called leptin<\/a> as a possible supportive molecule. Leptin is best known for helping the body regulate hunger\u2014and therefore weight. But it\u2019s also needed by the body\u2019s immune cells.<\/p>\n

Not only did the tumors the researchers analyzed have low concentrations of leptin, but the T cells in those tumors had high levels of the receptor<\/a> for the hormone. \u201cThis was especially true for exhausted T cells,\u201d explained Dr. Delgolffe.<\/p>\n

Studies in cell culture<\/a> showed that high levels of leptin enhance the ability of T cells to kill tumor cells. So the researchers tried delivering high doses of leptin directly into the bloodstream of mice bearing melanoma tumors. However, leptin delivered in this way had no effect on T cells within tumors.\u00a0<\/p>\n

To force leptin deep into the tumor microenvironment<\/a>, Dr. Delgoffe\u2019s team re-engineered their oncolytic virus to carry the gene for leptin production. Once inside a cancer cell, the virus would also produce leptin when it copied itself.<\/p>\n

When the researchers injected their dual-function virus directly into melanoma tumors in mice, the tumors shrank substantially, and about a quarter of the mice had a complete response<\/a> (that is, their tumors disappeared entirely). These mice lived substantially longer than mice injected with a control virus that didn\u2019t carry the leptin gene.\u00a0<\/p>\n

The leptin-expressing virus also improved survival in a mouse model<\/a> of aggressive pancreatic cancer.\u00a0<\/p>\n

In contrast, the leptin-expressing virus did not increase survival in mice bearing tumors already known to have a microenvironment supportive of T cells beyond what was seen with injection with the oncolytic virus that did not include the leptin gene.<\/p>\n

Potential for Preventing Cancer Recurrence<\/h2>\n

Injection with the leptin-expressing virus also seemed to serve as a cancer vaccine in some mice with melanoma. When the team injected the same tumor cells into mice that had experienced a complete response to the leptin-engineered virus, the immune systems of most of these mice prevented tumor regrowth.<\/p>\n

In the minority of mice that did have tumor regrowth, their tumors grew at slower rates. This suggests that the engineered virus had primed the immune system to remember and recognize the tumor cells (immune memory), Dr. Delgoffe said.<\/p>\n

\u201cIt\u2019s very exciting that there\u2019s some evidence of immune memory against tumors,\u201d Daschner said. \u201cIf this could work the way a vaccine works, hopefully patients would develop immunity that could prevent tumor recurrence.\u201d<\/p>\n

Dr. Delgoffe and his team are now investigating whether altering the leptin component of the virus could result in better responses. These tweaks include engineering leptin to make it better at finding and binding to T cells and to make it last longer in the tumor microenvironment. The researchers also plan to test the addition of other supportive molecules besides leptin to their virus.<\/p>\n

Further studies will be needed before the dual-functioning virus is ready for testing in people, including understanding if the virus could work as well if injected into the bloodstream as when injected into a tumor, Daschner explained. Direct injection into a tumor would not always be possible in people, he said.<\/p>\n

Viruses aren\u2019t the only microbe being studied as potential cancer treatments. NCI\u2019s Bugs as Drugs<\/a> initiative, for example, is supporting research into treatments based on bacteria and bacteriophages (tiny viruses that infect bacteria). \u201cIt\u2019s a very exciting class of potential new therapies,\u201d he said.<\/p>\n

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

October 15, 2019, by NCI Staff A cell infected by a vaccinia virus. Some of the oncolytic viruses being studied are engineered vaccinia viruses. Credit: J Cell Biol. April 2005. CC BY 4.0 Viruses engineered to kill cancer cells are already used to treat one form of skin cancer and are being widely tested as […]<\/p>\n","protected":false},"author":2,"featured_media":13753,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-13752","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\/13752","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=13752"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/13752\/revisions"}],"predecessor-version":[{"id":45728,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/13752\/revisions\/45728"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/13753"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=13752"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=13752"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=13752"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}