Tag Archive for: Keri Toner

Hyundai Hope on Wheels Logo

Oncologists receive Hyundai Hope on Wheels grants

Hyundai Hope on Wheels Logo

Keri Toner, M.D., and Hannah Kinoshita, M.D., both oncology researchers at Children’s National Hospital, were recently awarded Hyundai Hope on Wheels cancer research grants.

Dr. Toner, who is an attending physician in the Center for Cancer and Blood Disorders and the Center for Cancer and Immunology Research at Children’s National, received a $300,000 Hyundai Scholar Hope Grant that she will use to develop and functionally evaluate a novel T cell therapy which can be translated to the clinic for treatment of pediatric patients with acute myeloid leukemia (AML).

Currently, patients with relapsed AML have very poor outcomes and the success that T cell therapy has had in treating B-cell malignancies has not yet been achieved for AML. Dr. Toner’s goal is to try to overcome some of these barriers with a novel T cell therapy which combines both native and chimeric T cell receptors to target AML.

“There are currently critical barriers to the success of T cell therapies for the treatment of AML,” Dr. Toner explains. “Successful completion of this research would allow for translation of a novel CAR-TAA-T therapy to the clinic for the treatment of relapsed/refractory AML, which has very poor prognosis.”

Meanwhile, Dr. Kinoshita, a pediatric hematology oncology fellow at Children’s National, received a $200,000 Hyundai Young Investigator Grant. She will use the funds to evaluate the immunobiology of multi-antigen specific T cell therapy infused to patients to reduce the two most common causes of morbidity and mortality following hematopoietic stem cell transplant (HSCT) for malignant disease: relapse and infection.

The administration of multiantigen specific T cells targeting tumor and viral-associated antigens following stem cell transplant may serve to prolong remission of malignant disease and prevent and treat viral infections that can cause devastating disease in children. Dr. Kinoshita’s study will evaluate the anti-viral and anti-leukemia immune response in vivo following targeted T cell therapy.

“There have been incredible advancements in the field of pediatric oncology and bone marrow transplant over the past 20-30 years but there are still many areas in which we need to continue to improve,” Dr. Kinoshita says. “Our patients and their families go through so much to get into remission and it is devastating if they relapse or develop severe infectious complications. Adoptive immunotherapy is a promising tool in aiding to treat and prevent these complications, particularly for patients with high-risk hematologic malignancies.”

The Hyundai Scholar Hope Grants and the Hyundai Young Investigator Grants are competitive research grants that are peer-reviewed by the Hyundai Hope on Wheels Medical Advisory Committee, which is comprised of leading pediatric oncologists from children’s hospitals and research institutions nationwide. The grants are open to U.S.-based Children’s Oncology Group member institutions.

Hodgkin lymphoma cells

T-cell therapy alone or combined with nivolumab is safe and persistent in attacking Hodgkin’s lymphoma cells

Hodgkin lymphoma cells

Hodgkin’s lymphoma is a type of cancer that attacks part of the immune system and expresses tumor-associated antigens (TAA) that are potential targets for cellular therapies.

It is safe for patients with relapsed or refractory Hodgkin’s lymphoma (HL) to receive a novel tumor-associated antigen specific T-cell therapy (TAA-T) either alone or combined with a checkpoint inhibitor, nivolumab — a medication used to treat several types of cancer. The study, published in Blood Advances, further suggests that nivolumab aids in T-cell persistence and expansion to ultimately enhance anti-tumor activity. This offers a potential option for patients who do not have a durable remission with checkpoint inhibitors alone or are at a high risk of relapse after a transplant.

“The fact that this combination therapy is so safe was very encouraging for the treatment of patients with lymphomas,” said Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital. “In addition, this data allows us to consider this combination immunotherapy for other patients, including those with solid tumors.”

HL is a type of cancer that attacks part of the immune system and expresses tumor-associated antigens (TAA) that are potential targets for cellular therapies. While it may affect children and adults, it is most common in those who are between 20 and 40 years old. The survival rate for this condition has improved due to scientific advances.

A new approach in cancer therapy is the use of “checkpoint inhibitors,” which are a class of drugs that block some of the inhibitory pathways of the immune system to unleash a powerful tumor killing immune response. Similarly, T-cell therapies have also shown to enhance anti-tumor immune response. Therefore, combining these novel immune therapies is an attractive and targeted alternative to conventional untargeted therapies – such as chemotherapy and radiation – which not only kill the tumor cells but also can kill healthy cells and tissues.

“In five to 10 years we can get rid of chemotherapy and radiation therapy and have an immunotherapy focused treatment for this disease,” said Dr. Bollard.

To determine the safety of infusing TAA-T with and without checkpoint inhibitors, eight patients were infused with TAA-specific T-cell products manufactured from their own blood. Two other patients received TAA-T generated from matched healthy donors as adjuvant therapy after hematopoietic stem cell transplant. According to Dave et al., the TAA-T infusions were safe and patients who received TAA-T as adjuvant therapy after transplant remained in continued remission for over two years.

Of the eight patients with active disease, one patient had a complete response, and seven had stable disease at three months, three of whom remained with stable disease during the first year.

“Treating Hodgkin’s lymphoma with cellular therapy has not yet achieved the same success that we have seen for other lymphoma subtypes,” said Keri Toner, M.D., attending physician at Children’s National. “This study brings us closer to overcoming some of the current barriers by developing methods to improve the persistence and function of the tumor-specific T-cells.”

This study builds upon the researchers’ latest findings in another study, which demonstrated that TAA-T manufactured from patients were safe and associated with prolonged time to progression in solid tumors.

“The addition of a checkpoint inhibitor like Nivolumab to the TAA-T treatment is a powerful next step, but previously, the safety of this combination was unknown,” said Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, leader of the GMP laboratory and co-author of the study. “Now that we have demonstrated a safety profile, the next step will be to evaluate the efficacy of this combination in a larger subset of patients.”