Tag Archive for: Solid Tumors

little girl with cancer

A destination for pediatric oncology care: Children’s National Hospital’s T-cell therapy trials

When children are diagnosed with pediatric cancer, most doctors are forced to reach for the same standard therapies that were available decades ago. Research oncologists at Children’s National Hospital are changing that with clinical trials that will hopefully train the body’s immune system – specifically its T cells – to fight the tumors.

Holly Meany, M.D., and her colleague Amy Hont, M.D., oncologists and research scientists at the Center for Cancer and Immunology Research, have put together a pair of clinical trials that are investigating two pathways for using T cells to go after solid tumors.

“At Children’s National, we have a novel immunotherapy to offer to patients with relapsed or refractory solid tumors,” said Meany, director of the Solid Tumor Program. “This is a patient population who has failed standard therapy, so new technologies and treatments are always needed in this group.”

Where we started

Meany’s trial laid the foundation. She began the center’s research using a patient’s own blood sample to develop a targeted therapy and evaluate the safety and efficacy of this approach. In her study, scientists isolated the T cells, grew millions in a lab and reinfused them into the patient. The cells were replicated in an environment that was rich in three proteins that are commonly found on the surface of solid tumor cancer cells.

“Our hope and hypothesis are that when we give the T cells back to the patient, those T cells circulate and hunt down the cancer cells that have the tumor proteins,” Meany said. “We are hoping to use the patient’s own immune system to attack the cancer in an enduring way.”

Where we are headed

Hont’s phase 1 trial, which is currently recruiting participants, builds on Meany’s work using a healthy donor whose T cells have not been impacted by chemotherapy or other treatments. The cells can be prepared, stored and readily available for patients who need them. They are also matched through specific proteins on the patient’s own cells to bolster their effectiveness. The participants in this trial have Wilms tumors, rhabdomyosarcoma, neurosarcoma, soft tissue sarcoma or neuroblastoma, but conventional therapies including chemotherapy, radiation or surgery were unable to fully treat the disease.

In both studies, Hont said that the T cells have been given in an outpatient setting with fewer side effects compared to other cancer treatments aimed at high-risk malignancies.

“This allows patients to really maintain a good quality of life during a particularly hard time,” Hont said. “Also, these T cells are designed to act in the body the way that our immune system acts in a physiologic way. This means patients typically don’t have the severe side effects that we think of with chemotherapy or other therapies.”

Children’s National leads the way

The team at Children’s National is one of the few in the country to offer this kind of T-cell therapy for solid tumors. “Immunotherapy has been challenging for this patient population because the tumors are adept at finding out ways to evade treatment,” Hont said. “Giving patients a chance to receive a targeted T-cell therapy, while also maintaining a high quality of life, is something that’s special here.”

MRI Room

Using high-intensity focused ultrasound to treat solid tumors

“I think high-intensity focused ultrasound is a really exciting technology that will allow for a different paradigm of how we think about treating solid tumors, both in a local and in a systemic way,” says AeRang Kim, M.D., oncologist at Children’s National Hospital. Dr. Kim explains high-intensity focused ultrasound (HIFU) and how she and her team have used this technology to treat pediatric solid tumors.

HIFU is energy that can be focused on any region of the body. It allows doctors to provide different types of energy in varying amounts, and it’s typically coupled with magnetic resonance imaging, which allows for precise, focused energy to specific areas with accuracy and temperature guidance.

Children’s National was one of the first pediatric centers to open a clinical trial for the treatment of pediatric solid tumors. Since then, we’ve opened several other clinical trials and combined them with targeted chemotherapy for the ablation of benign tumors and malignant solid tumors. We are one of the few institutions that have this study open and we are leading the clinical trials and coordinating them with other institutions across the country.

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

Dr. Bollard and her laboratory

Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

Dr. Bollard and her laboratory

Cancer Grand Challenges NexTGen team members (left to right): Amy Hont, M.D., AeRang Kim, M.D., Nitin Agrawal, Ph.D., Catherine Bollard, M.D., M.B.Ch.B., Conrad Russell Cruz, M.D., Ph.D., Patrick Hanley, Ph.D., and Anqing Zhang.

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, has been selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children. Cancer Grand Challenges is a global funding platform, co-founded by Cancer Research UK and the National Cancer Institute in the U.S., that supports a community of diverse, global teams to come together, think differently and take on some of cancer’s toughest challenges.

The Cancer Grand Challenges NexTGen team, co-led by University College London’s Martin Pule, M.D., will be working to develop next-generation cell therapies for children with solid cancers. Cancer is a leading cause of death by disease in children worldwide. Although survival has increased for some pediatric cancers, such as blood cancers, survival for some solid tumors has seen little improvement for more than 30 years. The team hopes to build a much deeper understanding of childhood cancers and develop and optimize novel therapies for children with solid tumors, ultimately hoping to improve survival and diminish the lifelong toxicities often experienced by survivors.

“With our Cancer Grand Challenge, we hope to bring next-generation CAR T-cell therapies to children with solid tumors,” said Dr. Bollard. “What excites me most is the energized, passionate group of people we’ve brought together to take this challenge on. Big problems remain to be addressed, but we believe they can be solved, and that we’re the team to solve them.”

“NexTGen represents crucial and overdue work. It has hope written all over,” said Sara Wakeling, patient advocate on the team and CEO and co-founder of Alice’s Arc, a children’s charity for rhabdomyosarcoma. “NexTGen hopes to transform the way these aggressive solid tumors are treated with less toxic side-effects, giving the children a real chance at growing up and realizing their potential. I’m so proud to be part of this exceptional team of scientists, clinicians and advocates who want to change the story for those diagnosed.”

The NexTGen team unites scientists and clinicians with expertise in immunology, proteomics, mathematics and more, across eight institutions throughout the U.S., U.K. and France. The Children’s National investigators that will also join are:

  • Nitin Agrawal, Ph.D., associate professor in the Center for Cancer and Immunology Research at Children’s National.
  • Conrad Russell Cruz, M.D., Ph.D.,principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies at Children’s National.
  • Patrick Hanley, Ph.D., chief and director of the cellular therapy program at Children’s National and leader of the Good Manufacturing Practices laboratory.
  • Amy Hont, M.D., oncologist in the Center for Cancer and Immunology Research at Children’s National.
  • AeRang Kim, M.D., oncologist in The Center for Cancer and Blood Disorders at Children’s National.
  • Holly Meany, M.D., oncologist in The Center for Cancer and Blood Disorders at Children’s National.
  • Anqing Zhang, biostatistician in the Biostatistics and Study Methodology Department at Children’s National.

The team, co-funded by Cancer Research UK, the National Cancer Institute and The Mark Foundation for Cancer Research, aims to bring much needed new treatments to children with solid cancers.

The NexTGen team is one of four new teams announced today as part of Cancer Grand Challenges, representing a total investment of $100m to diverse, global teams to take on some of the toughest challenges in cancer research.

“Cancer is a global issue that needs to be met with global collaboration. This investment in team science encourages diverse thinking to problems that have long hindered research progress,” said David Scott, Ph.D., director of Cancer Grand Challenges, Cancer Research UK. “Cancer Grand Challenges provides the multidisciplinary teams the time, space and funding to foster innovation and a transformative approach. NexTGen is one of four newly funded teams joining a scientific community addressing unmet clinical needs across cancer research.”

Find out more

Cancer Grand Challenges supports a global community of diverse, world-class research teams with awards of £20m/$25m to come together, think differently and take on cancer’s toughest challenges. These are the obstacles that continue to impede progress and no one scientist, institution or country will be able to solve them alone. Cancer Grand Challenges teams are empowered to rise above the traditional boundaries of geography and discipline.

Founded by the two largest funders of cancer research in the world – Cancer Research UK and the National Cancer Institute* in the U.S. – Cancer Grand Challenges aims to make the progress against cancer we urgently need. Cancer Grand Challenges currently supports more than 700 researchers and advocates across 10 countries, representing 11 teams are supported to take on 10 of the toughest challenges in cancer research.

The Cancer Grand Challenges NexTGen team, announced June 16, 2022, is taking on the initiative’s Solid Tumours in Children challenge. It is led by Dr. Bollard (Children’s National) and Dr. Pule (University College London), along with 23 co-investigators and 7 patient advocates, and is spread across eight institutions across the U.S., U.K. and France: Cardiff University; Children’s Hospital of Philadelphia; Children’s National Hospital; INSERM; the Institute of Cancer Research; Stanford Medicine; Stanford University; University College London. The Cancer Grand Challenges NexTGen team is funded by Cancer Research UK, the National Cancer Institute in the U.S. and The Mark Foundation for Cancer Research.

*The National Cancer Institute is part of the National Institutes of Health.

 

T cell

Children’s National Hospital scientists shortlisted for Cancer Grand Challenges funding

T cell

If successful, the team would seek to tackle the challenge of solid tumors in children. The vision is to bring engineered T-cell therapies to the routine treatment of these children within a decade.

A diverse, global team of scientists, led by University College of London and Children’s National Hospital/George Washington University, has been selected for the final stages of Cancer Grand Challenges – and is in with a chance of securing a share of £80 million (c.$111 million) of funding to take on one of cancer’s toughest problems.

Nearly 170 teams submitted ideas for this round of awards, and the NGTC team, which stands for ‘Next Generation T-cell therapies for childhood cancers, led by Martin Pule, Ph.D., University College of London, and Catherine Bollard, M.B.Ch.B., M.D., Children’s National Hospital and George Washington University, is one of 11 shortlisted groups.

The team draws together a unique set of expertise, uniting researchers from the U.K., U.S. and France. Other team members from Children’s National include Conrad Russell Cruz, M.D., Ph.D., principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies, and Nitin Agrawal, Ph.D., associate professor in the Center for Cancer and Immunology Research (CCIR). Up to four winning teams will be announced in early 2022.

If successful, the NGTC team would seek to tackle the challenge of solid tumors in children. The team says that the scientific and medical communities are beginning to understand that solid tumors in children are very different from those in adults – if they could understand more about these differences and find new ways to target them, they could create new ways to better treat children’s cancers.

The NGTC team’s vision is to bring engineered T-cell therapies to the routine treatment of these children within a decade.

Through a series of ambitious studies, the team hopes to identify suitable, pediatric tumor-specific targets for engineered T-cells, including previously unexplored options like glycolipids or the immunopeptidome. They also hope to explore whether treatment effectiveness can be boosted by modulating the tumor microenvironment – which can inhibit T-cell therapies but is yet to be suitably studied in children’s cancers. The team has a strong translational focus and the most promising new treatment avenues would be explored in preclinical and early clinical studies.

“We’re tremendously excited to have this opportunity to work together and strive closer to our vision – to improve the lives of the patients we serve,” says joint team lead Dr. Bollard, who is also the director of the Center for Cancer and Immunology Research at Children’s National.

“This round of Cancer Grand Challenges has demonstrated the fresh thinking that can be sparked when global teams unite across disciplines to bring new perspectives to tough challenges,” says Dr. David Scott, Ph.D., director of Cancer Grand Challenges. “We were thrilled to receive such a strong response from the global research community.”

Find out more at cancergrandchallenges.org.

Holly Meany

TAA-Ts as therapy for tumors

Holly Meany

“The T cell immunotherapy regimen resulted in prolonged disease stabilization in patients who previously experienced rapid tumor progression,” says Holly Meany, M.D. “The therapy could prove to be an important component of immunotherapy for patients with solid tumor malignancies.”

In a study published in the Journal of Clinical Oncology, researchers from Children’s National Health System uncovered tumor-associated antigen cytotoxic T cells (TAA-Ts) that represent a new and potentially effective nontoxic therapeutic approach for patients with relapsed or refractory solid tumors.

The Phase 1 study led by Children’s National pediatric oncologists Holly Meany, M.D., and Amy B. Hont, M.D., represented the first in-human trial investigating the safety of administering TAA-Ts that target Wilms Tumor gene 1, a preferentially expressed antigen of melanoma and survivin in patients with relapsed/refractory solid tumors.

“These are exciting clinical results using a novel ‘first in-human’ T cell therapy,” said Catherine Bollard, MB.Ch.B., M.D., director of the Center for Cancer and Immunology Research at Children’s Research Institute. “This T cell therapy was safe and appeared to prolong patients’ time to progression which suggests that we can now use this novel treatment as a combination therapy to hopefully achieve long-term remissions in pediatrics and adults with relapsed/refractory solid tumors.”

During the Phase 1 trial, TAA-Ts products were generated from autologous peripheral blood and were infused over three dose levels. Patients were then eligible for up to eight infusions that were administered four to seven weeks apart.

Of the 15 evaluable patients, 11 were with stable disease or better at 45 days post-infusion and were defined as responders. Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival rate of 73% after TAA-Ts infusion, an improvement as compared with prior therapy.

Overall, the Phase 1 trial of TAA-Ts resulted in safely induced disease stabilization and was associated with antigen spreading and a reduction in circulating tumor-associated antigen DNA levels in patients with relapsed/refractory solid tumors before infusion.

“The T cell immunotherapy regimen resulted in prolonged disease stabilization in patients who previously experienced rapid tumor progression,” said Dr. Meany. “The therapy could prove to be an important component of immunotherapy for patients with solid tumor malignancies,” she added.

The other researchers that contributed to this work are as follows: Amy B. Hont, M.D.; C. Russell Cruz, M.D., Ph.D.; Robert Ulrey, M.S.; Barbara O’Brien, B.S.; Maja Stanojevic, M.D.; Anushree Datar, M.S.; Shuroug Albihani, M.S.; Devin Saunders, B.A.; Ryo Hanajiri, M.D., Ph.D.; Karuna Panchapakesan, M.S.; Sam Darko, M.S.; Payal Banerjee, M.S.; Maria Fernanda Fortiz, B.S.; Fahmida Hoq, MBBS, M.S.; Haili Lang, M.D.; Yunfei Wang, Dr.PH.; Patrick J. Hanley, Ph.D.; Jeffrey S. Dome, M.D., Ph.D.; Catherine M. Bollard, M.D.; and Holly J. Meany, M.D.