Finding the answer to children's leukemia:
Scott & White researcher searching for the key that will unlock leukemia

By Patricia K. Benoit

A Scott & White physician is hunting for the key to unlock the secret to stopping or killing children's leukemias for good and, in turn, learning more about switching off adult leukemia.

Scott & White and the Department of Pediatrics have one of the few laboratories in the nation devoted primarily to treating childhood leukemia. The focus is on novel applications of monoclonal antibodies that locate tumor cells and either arrest there development or deliver tumor-killing substances without harming healthy cells.

"We're moving away from the 'magic bullet' concept," said Larry Herrera, M.D., Scott & White physician-scientist. "I think of a tumor cell as having keyholes, called receptors. We are finding the right keys to turn off cancer cells. This would represent a marked advancement because such a treatment would be able to turn off tumors selectively without affecting healthy organs."

Leukemia is the most common form of cancer in children. The cancer starts in the bone marrow and can spread to the lymph nodes, spleen, liver and central nervous system. Medical researchers have made quantum leaps in treating children's leukemia since the 1950s, when it was uniformly fatal. Today, on average 75 to 80 percent of children survive. But what about the remaining 20 percent whose disease goes into remission, only to return again and again?

"Now is the time for us to make another real advancement in treating children's leukemia and not rest on what we've done," Dr. Herrera said. "We need to stop saying, 'Look at the advancements we've made' and start asking ourselves, 'Why aren't we curing 100 percent of these kids?' It's possible. So why aren't we?"

During his five years at Scott & White, his work has evolved from bench to bedside. First, he and his research team cultivated actual leukemia cells in the laboratory to test the antibodies. Then, they used these antibodies to successfully treat mice with leukemia. "The antibodies could be used with chemotherapy, still the "gold standard" treatment, to enhance and strengthen its beneficial effects." In turn, physicians could use less chemotherapy, and the patients would have fewer reactions. "We have already shown that antibody therapy can help sick children go into remission and be well enough to undergo bone marrow transplants," he added.

Funded by a five-year grant from the National Institutes of Health, Dr. Herrera and his team of physicians and scientists are conducting a Phase I studies to determine appropriate dosages of antibody therapy in patients who have exhausted all other treatments.

Researchers meet weekly with other cancer team members, especially pediatric oncology-hematology specialists Dick Young Suh, M.D., Ph.D., and Latha Prasannan, M.D., to discuss patients who would benefit from research.

So far, the results have been promising with some patients going into remission. Medical centers in Germany, Florida, Colorado, Minnesota and Dallas are participating with Scott & White.

"Here we are, possibly curing some of these kids," Dr. Herrera said. "We won't know for certain for years. One child in Germany went into remission and qualified for a bone marrow transplant. He appears to be cured at this time and has no evidence of disease. We have other children who weren't supposed to live beyond this past Christmas. We treated them with two courses of the antibody therapy, and they are in complete remission with no evidence of disease."

To bolster research in adult's and children's cancers, Scott & White has recruited an internationally recognized cancer researcher, Arthur E. Frankel, M.D. He and his research team will also guide Scott & White into partnerships with industry, continuing NIH funding, patient referrals and global attention to develop and market cancer-fighting treatments.

"Our goal is to make sure all children with cancer will survive. We hope to engage in research and develop technologies to target pediatric cancers and offer treatments that are not offered any place in the world," Dr. Suh said.

Although Dr. Frankel's research involves mostly adults, this collaboration will benefit children, too. Dr. Herrera expects three more study phases to follow, each expanding the numbers of patients and scope of the trial. Dr. Herrera and Scott & White hope to create antibodies that can be available to children worldwide. Dr. Herrera is confident that this research will eventually be applicable to adults. It could also lead to greater understandings of acute myelogenous leukemia, T-cell leukemia and chronic lymphocytic leukemia.

Dr. Frankel's arrival in Central Texas is a boon to cancer patients of all ages. He sees Scott & White with its vast clinical expertise and large patient volume as the ideal place to translate basic science research into active clinical treatment in the shortest possible time.

"This partnership will help us translate what is happening in laboratory and bring it right where physicians successfully treat patients," Dr. Herrera added.

SCOTT & WHITE PHYSICIAN SCIENTIST
DEVELOPS RESEARCH PROGRAM TO FIGHT CHILDHOOD LEUKEMIA

Ten-year-old Antonella Otiniano was a beautiful, smart, sweet child. She had a loving family, wonderful friends and great hope for the future. She also had leukemia. The young girl who had such passion for life, lost her battle against the leukemia that destroyed her body.

Unfortunately, hers is not the only heartbreaking story of a child losing his or her life to an invisible killer. For children under the age of 15, cancer is the number one cause of death. But a physician scientist at Scott & White is on the path to finding new ways to change that number, and give more of our children a chance to see the future.

Larry Herrera, M.D., part of the pediatric oncology team at Scott & White, has developed a l cancer research program for children with leukemia who are no longer responding to chemotherapy. After completing fellowships in pediatric hematology/oncology cancer research, Dr. Herrera came to Scott & White to develop the program, which is focused on the development and testing of investigational antibodies to treat relapsed Acute Lymphoblastic Leukemia (ALL). In part of his research, Dr. Herrera has found that two immunotoxins (antibodies linked to toxins) can kill leukemia cells, and that these are even more potent and specific than chemotherapy.

"We want to understand the effect of immunotoxins and antibodies on tumor cells," said Dr. Herrera, the study's principal investigator. "We have found that these antibodies can cause tumor cells to stop dividing, and in essence kill the cells. We want to know how to increase that effect."

Dr. Herrera added that his research also focuses on finding ways to use these antibodies in conjunction with or even instead of chemotherapy.

Currently, Dr. Herrera is conducting a Phase I study for children with leukemia who have not responded to chemotherapy or other treatments. The goal of this phase is to determine the safety of the antibodies. About 15 to 20 children are expected to be enrolled in the study during the next three to four years.

In addition to Scott & White, the Children's Hospital and Clinic in Minneapolis, the University of Texas Southwestern, and Morris Clinics in Florida are participating in the study, with Dr. Herrera leading the activities and coordinating results for all.

"I really feel this treatment is the future," Dr. Herrera said. "I foresee that many cancers that are currently treated with chemotherapy can be treated with antibody therapy. I believe these kids can be cured.

DR. HERRERA - PEDI ONCOLOGY GRANT

It's a fight that many say can never be won, but one local physician-scientist is doing all he can to make sure it can be beaten. Larry Herrera, M.D., a pediatric oncologist at Scott & White has dedicated his professional life to finding another cure for childhood leukemia, and the research he is doing is putting him on the right track.

Dr. Herrera has developed a cancer research program focused on the development and testing of investigational antibodies to treat relapsed Acute Lymphoblastic Leukemia (ALL). Dr. Herrera has found that two immunotoxins (antibodies linked to toxins) can kill leukemia cells, and these immunotoxins are more potent and specific than chemotherapy.

During the past year and a half Dr. Herrera has seen wonderful results, and he's not the only one who has noticed the progress. Recently, Dr. Herrera was given $500,000 to support his research efforts. The money came from Wayne Hughes, a businessman and entrepreneur in California, who lost a son to leukemia.

"The donation from Mr. Hughes has given our project a much needed boost," Dr. Herrera said. "Of the $500,000 he donated, I am keeping $250,000 here at Scott & White, and the rest will be spent to support the production of the immunotoxins that we are testing in these trials. Without his donation, I do not think we would have been able to continue with this trial. It has helped us buy equipment and helped support the staff doing the work. This is a wonderful example of how these funds can really make a difference."

Currently, Dr. Herrera is conducting a Phase I study for children with leukemia who have not responded to chemotherapy or bone marrow transplants. The goal of this study is to determine the safety of the antibodies. So far, six children have been treated and four have responded. One child did achieve a complete remission.

"We have been very pleased with the results, but not completely surprised," Dr. Herrera said. "I've always known this could be a viable treatment, and the results we are seeing so far are very exciting. You don't normally see results such as these in a Phase I trial, and to have achieved a remission is just wonderful."

Dr. Herrera says his goal is to treat 20 children in the Phase I Study, which he hopes to complete over the next year and a half to two years.

In addition to Scott & White, the Children's Hospital in Los Angeles, Children's Hospital and Clinics in Minneapolis, the University of Texas Southwestern Medical Center in Dallas, Emory University and Nemours Children's Clinics in Florida are participating in the study.

Dr. Herrera, who has also received a grant from the National Institutes of Health, says after the Phase I trial is finished, Phase II will focus on finding the best way to combine the antibody-based agents with chemotherapy, thereby attacking the cancer with two very different therapies at one time. But while his research continues, Dr. Herrera says his project is always in danger of being cut short.

"The one thing that I fear about this project is that these immunotoxins may never see the light of day without adequate financial support. We are making wonderful progress on something that no one else is doing. But it's a venture that is very expensive and very time consuming, and without funds like those from Mr. Hughes, we cannot continue. Our local community has been very supportive of our research, and I truly think we are on the right track to developing a successful treatment for childhood leukemia and possibly other forms of childhood cancer as well."