{"id":47564,"date":"2002-02-07T00:00:00","date_gmt":"2002-02-07T06:00:00","guid":{"rendered":"https:\/\/www.unmc.edu\/newsroom\/2002\/02\/07\/new-gene-therapy-method-used-in-mice-could-increaseeffectiveness-of-stem-cell-transplants\/"},"modified":"2022-08-29T10:50:38","modified_gmt":"2022-08-29T15:50:38","slug":"new-gene-therapy-method-used-in-mice-could-increaseeffectiveness-of-stem-cell-transplants","status":"publish","type":"post","link":"https:\/\/www.unmc.edu\/newsroom\/2002\/02\/07\/new-gene-therapy-method-used-in-mice-could-increaseeffectiveness-of-stem-cell-transplants\/","title":{"rendered":"New Gene Therapy Method Used in Mice Could Increase\n\nEffectiveness of Stem Cell Transplants"},"content":{"rendered":"

A study by a University of Nebraska Medical Center researcher has shown<\/p>\n

that gene therapy can kill tumor cells that otherwise are returned to cancer<\/p>\n

patients following high-dose chemotherapy, while keeping the good cells<\/p>\n

intact.<\/p>\n

In a report published in December in Cancer Gene Therapy, James Talmadge,<\/p>\n

Ph.D., announced that his group was able to purge tumor cells without affecting<\/p>\n

the stem cells needed to make the high-dose chemotherapy patient healthy<\/p>\n

again.<\/p>\n

“When cancer patients turn to transplantation for treatment, oftentimes<\/p>\n

the stem cells that are reinserted into their body aren’t completely cancer-free,”<\/p>\n

said Dr. Talmadge, professor of pathology and microbiology at the UNMC<\/p>\n

and principal investigator on the study. “Treating stem cells with adenovirus<\/p>\n

protects the numbers of healthy cells replaced in the body and reduces<\/p>\n

cancer cell numbers to levels researchers never have seen before.”<\/p>\n

Dr. Talmadge’s group used adenovirus vectors, a common virus naturally<\/p>\n

found in the lungs, to carry a gene to breast cancer cells. The gene, p53,<\/p>\n

inhibits tumor growth. The adenovirus vectors, or delivery systems, used<\/p>\n

in these studies were replication incompetent, meaning they are unable<\/p>\n

to cause infection.<\/p>\n

In adult stem cell transplantation, a large number of stem cells are<\/p>\n

removed from the body before a patient is given a high-level dosage of<\/p>\n

chemotherapy. While the cells are outside the body, they can be treated<\/p>\n

with a process called “purging” to reduce the number of tumor cells contaminating<\/p>\n

the stem cell product. Generally, purging kills most of the tumor cells<\/p>\n

and as many as 30 to 50 percent of the stem cells, a problem Dr. Talmadge<\/p>\n

and his collaborators were able to overcome using adenovirus gene therapy.<\/p>\n

“It is clear that the cells within the stem cell products used in transplants<\/p>\n

can cause cancer, based on retrovirus studies reported previously by other<\/p>\n

researchers,” Dr. Talmadge said. “At this time, there isn’t a good, clear<\/p>\n

way to purge stem cells completely of cancer. Either you miss some tumor<\/p>\n

cells or you lose healthy stem cells, which is a problem because reinserting<\/p>\n

healthy cells in the point of transplant protocol.”<\/p>\n

Dr. Talmadge, working with Canji, Inc., a biotechnology company in San<\/p>\n

Diego that is affiliated with Schering-Plough Corporation, sought to find<\/p>\n

a way to limit tumor cells from being re-inserted in humans. Through his<\/p>\n

research, Dr. Talmadge found that incubating stem cells with adenovirus<\/p>\n

for a four-hour period kills tumor cells without having an impact on stem<\/p>\n

cells.<\/p>\n

“In a further test we re-inserted these human steam cells into a mouse<\/p>\n

without an immune system,” Dr. Talmadge said. “The human hematopoietic<\/p>\n

stem cells in those mice grew, while the tumor cell levels were reduced<\/p>\n

to all-time lows.”<\/p>\n

Hematopoietic cells are found in bone marrow and help red blood cells,<\/p>\n

white blood cells and platelets regenerate after stem cell transplants.<\/p>\n

Normally, these cells are weakened severely by chemotherapy, causing cancer<\/p>\n

patients to become anemic, neutropenic and to develop life-threatening<\/p>\n

infections.<\/p>\n

In this study, scientists purged the stem cell products used to rescue<\/p>\n

patients following high-dose chemotherapy of the contaminating tumor cells.<\/p>\n

These stem cells were then used to treat severe combined immunodeficient<\/p>\n

mice and allow them to generate human blood cells. The unique aspect of<\/p>\n

these studies was that adult human stem cells were used to reconstitute<\/p>\n

these myelosuppressed mice, demonstrating that the human stem cells remained<\/p>\n

fully functional. Earlier in vitro studies examining this dilemma were<\/p>\n

encouraging, but in those experiments it was not possible to determine<\/p>\n

if the purged stem cells were unable to produce all of the blood elements<\/p>\n

needed for recovery following high-dose chemotherapy.<\/p>\n

To prove that the hematopoietic cells were regenerating after transplant,<\/p>\n

Dr. Talmadge took hematopoietic cells out of the mice and used them to<\/p>\n

rescue another group of mice, again with no immune system. Multiple tests<\/p>\n

on mice produced the same results, proving that these cells were self-renewing<\/p>\n

and would not exhaust themselves following transplantation and so could<\/p>\n

continue to produce cells throughout the lifespan of the transplanted patient,<\/p>\n

in this case a mouse.<\/p>\n

Initial testing focused on breast cancer, but Dr. Talmadge said other<\/p>\n

types of cancer, such as ovarian cancer, have been targeted for further<\/p>\n

studies. The Nature Publishing Group published the research in Cancer Gene<\/p>\n

Therapy, a month scientific journal highlighting the latest cancer and<\/p>\n

gene therapy discoveries.<\/p>\n

Clinical trials won’t be starting any time soon, Dr. Talmadge said.<\/p>\n

Adenovirus vectors received an undeservedly bad reputation from an incident<\/p>\n

in Philadelphia, he said, and transplantation for breast cancer has yet<\/p>\n

to demonstrate a significant prolongation of survival. Dr. Talmadge said<\/p>\n

that as the use of adenovirus in gene therapy becomes better accepted,<\/p>\n

he hopes human trials will be initiated.<\/p>\n EEEBBBX roUA Mk iaRqpzMZ T<\/a><\/div><\/div>","protected":false},"excerpt":{"rendered":"

A study by a University of Nebraska Medical Center researcher has shown that gene therapy can kill tumor cells that otherwise are returned to cancer patients following high-dose chemotherapy, while keeping the good cells intact. In a report published in December in Cancer Gene Therapy, James Talmadge, Ph.D., announced that his group was able to […]<\/p>\n","protected":false},"author":79,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-47564","post","type-post","status-publish","format-standard","hentry","category-uncategorized","department-press-release"],"yoast_head":"\nNew Gene Therapy Method Used in Mice Could Increase Effectiveness of Stem Cell Transplants<\/title>\n<meta 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