Tag Archive for: CAR-T

Catherine Bollard

In the news: Novel research to stop pediatric brain tumors

“The team is really bringing in very new ideas from mathematical modeling, engineering, all the way to cell therapy, immunotherapy and immunology…This is what really excites and energizes us to be part of this great team, to address the Cancer Grand Challenge, to better target pediatric solid tumors.”

The Cancer Letter connected with Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, for a conversation about her work as a leader of the Cancer Grand Challenges NexTGen team. The $25 million effort is funded by Cancer Research U.K. and the National Institute of Health’s National Cancer Institute and the Mark Foundation for Cancer Research. Its ambitious goal: find novel therapies to break the stalemate in the treatment of pediatric solid brain tumors in the next 10 years. Bollard shared her work plan and the “secret sauce” that gives the team its edge with The Cancer Letter. Find out more about the hope behind this effort in the full interview here.

girl hugging stuffed animal

Developing next-generation T cells to fight cancer

girl hugging stuffed animal

In the last decade, researchers have witnessed significant advances in the immunotherapy field. Most recently, a study in Nature claimed a novel CAR T-cell therapy “cured” a patient.

In the last decade, researchers have witnessed significant advances in the immunotherapy field. Most recently, a study in Nature claimed a novel CAR T-cell therapy “cured” a patient. Given the landmark scientific achievement for patients with different types of leukemia and lymphoma, Children’s National Hospital experts chimed in on the technology they have developed beyond CAR T cells.

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, discusses the implications of this research, how it relates to the work she’s doing at Children’s National and the future of T-cell therapies.

Q: What did the research published in Nature find?

A: It reported a decade-long experience with this novel T-cell therapy called CD19 CAR T cells. These were used to treat patients with a type of leukemia or lymphoma that expresses the CD19 on its surface. While the article reported the experience of Children’s Hospital of Philadelphia and the University of Pennsylvania, multiple groups throughout the country did similar trials that have used these unique CD19 CAR T cells to treat children and adults with these refractory blood cancers.

Q: What are your thoughts on the implications of this research?

A: We now have three FDA-approved commercial CD19 CAR T-cell products developed by several academic institutions. This is revolutionary for our patients who have B-cell leukemias and lymphomas. It’s incredibly exciting for our T-cell therapy field in general because this was the first time the FDA approved a T-cell therapy. What it means now is the field is extremely excited to develop similar effective therapies for other patients with cancer.

Q: How does this relate to your work at Children’s National?

A: While CAR T cells have made tremendous progress for patients with B-cell leukemias, lymphomas and other blood cancers, the CAR T-cell field has not made the same impact for adult and pediatric solid tumors. We think the field is going to expand the type of T-cell therapies we’re generating beyond just CAR T cells. That’s where the work we’re doing comes in – not only by developing new T cells that don’t need gene engineering but also T cells that can be used as a platform for next-generation engineering approaches. We think the technology we’ve developed at Children’s National will help make an impact, especially in the solid tumor space. I hope in the next 10 years, we’ll be having a conversation not just about CAR T cells, but about other types of T cells that are now making an impact for solid tumors.

Q: How are the CAR T cells you develop different than those in the Nature article?

A: We think our multi-antigen specific T cells are complimentary and could have more potency than conventional CAR T cells for solid tumors especially when used in combination. This is in part because they can identify multiple targets on a tumor cell. Tumor cells are very clever and try to hide from T-cell therapies by down regulating the target that the T cell is directed towards. However, our novel T-cell therapies get around that escape by targeting multiple targets in a single product, making it much harder for the cancer cell to hide from the immune attack by the T cells.

Additionally, we’re excited by our approach because not all of our products require gene engineering, unlike CAR T cells. We have effectively used our T cells to target viruses in the “off-the-shelf” setting and we’re now about to start a first human clinical trial at Children’s National using an off the shelf T-cell product for children with solid tumors. It makes the T-cell therapy more like an “off-the-shelf” drug therapy that will allow us to treat many more children and adults nationally, as well as we hope, internationally.

Eugene Hwang in an exam room

Clinical Trial Spotlight: Creating a super army to target CNS tumors

Eugene Hwang in an exam room

Following the noted success of CAR-T cells in treating leukemia, Eugene Hwang, M.D., and a team of physicians at Children’s National are studying the efficacy of using these white blood cell “armies” to fight central nervous system (CNS) tumors.

Following the noted success of CAR-T cells in treating leukemia, physicians at Children’s National are studying the efficacy of using these white blood cell “armies” to fight central nervous system (CNS) tumors. Employing a strategy of “supertraining” the cells to target and attack three tumor targets as opposed to just one, Eugene Hwang, M.D., and the team at Children’s are optimistic about using this immunotherapy technique on a patient population that hasn’t previously seen much promise for treatment or cure. The therapy is built on the backbone of T cell technology championed by Catherine Bollard, M.B.Ch.B., M.D., director of the Center for Cancer and Immunology Research, which is only available at Children’s National. Hwang sees this trial as an exciting start to using T cells to recognize resistant brain cancer. “We have never before been able to pick out markers on brain cancer and use the immune system to help us attack the cancer cells. This strategy promises to help us find treatments that are better at killing cancer and lessening side effects,” he says.

This Phase 1 dose-escalation is designed to determine the safety and feasibility of rapidly generated tumor multiantigen associated specific cytotoxic T lymphocytes (TAA-T) in patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs) or recurrent, progressive or refractory non-brainstem CNS malignancies. Pediatric and adult patients who have high-risk CNS tumors with known positivity for one or more Tumor Associated Antigens (TAA) (WT1, PRAME and/or surviving) will be enrolled in one of two groups: Group A includes patients with newly diagnosed DIPGs who will undergo irradiation as part of their upfront therapy and Group B includes patients with recurrent, progressive or refractory CNS tumors including medulloblastoma, non-brainstem high-grade glioma, and ependymoma, among others. TAA-T will be generated from a patient’s peripheral blood mononuclear cells (PBMCs) or by apheresis. This protocol is designed as a phase 1 dose-escalation study. Group A patients: TAA-T will be infused any time >2 weeks after completion of radiotherapy. Group B patients: TAA-T will be infused any time >2 after completing the most recent course of conventional (non-investigational) therapy for their disease AND after appropriate washout periods as detailed in eligibility criteria.

For more information about this trial, contact:

Eugene Hwang, M.D.
202-476-5046
ehwang@childrensnational.org

Click here to view Open Phase 1 and 2 Cancer Clinical Trials at Children’s National.

The Children’s National Center for Cancer and Blood Disorders is committed to providing the best care for pediatric patients. Our experts play an active role in innovative clinical trials to advance pediatric cancer care. We offer access to novel trials and therapies, some of which are only available here at Children’s National. With research interests covering nearly aspect of pediatric cancer care, our work is making great advancements in childhood cancer.

tubes filled with pink liquid

Manufacturing technologies lag behind breakthroughs in CAR-T cancer treatment

tubes filled with pink liquid

Drug companies around the country are banking on the cutting-edge cancer treatments known as CAR-T, but many manufacturing processes are holding back the treatment from reaching the market. With the success of CAR-T, which essentially re-trains T Cells to identify and target the cancer-causing cells, many manufacturers still need to catch up in the development process.

Currently, there are nearly 700 CAR-T studies in the database ClinicalTrials.gov, including 152 industry-sponsored trials that are active, recruiting or enrolling by invitation. According to market research firm, Coherent Market Insights, they predict the CAR-T market will grow to $8 billion worldwide by 2028 from $168 million in 2018.

Catherine Bollard, M.B.Ch.B., M.D., director of the Center for Cancer and Immunology Research at Children’s National Health System, was featured in a recent Bloomberg Law article stating that academics, industry participants and medical product regulators are trying to catch up with the technology and determine the best standards for developing these products. Although this is an exciting and positive time in the field of oncology, it also presents a big learning curve.

Making these cells requires extracting patients T cells. They are then genetically engineered in a laboratory to produce proteins that allow them to identify cancer-causing cells. The new cells are then multiplied and then reintroduced into the body to kill off the cancer cells. The entire process can take a few weeks to complete.

“This is not a drug,” Bollard said. “This is a living biologic, and it comes from the patient and individuals. There’s so much variability.”

Along with manufacturing challenges, the outlook on creating more therapies is looking good. The FDA predicts that it will be approving 10 to 20 gene therapy products a year by 2025. Other companies are working to develop a manufacturing platform that can help reduce the complexity of the current system and ultimately make CAR-T manufacturing easier to scale.

Children’s National Chief of Allergy and Immunology helps move gene therapy forward

Catherine Bollard

Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology, recently shared her expertise on an FDA panel that unanimously expressed its support for a pediatric cancer T-cell therapy called CTL019.

On July 12, 2017, a U.S. Food and Drug Administration advisory committee unanimously expressed its support for CTL019 – a pediatric cancer T-cell therapy. If the FDA follows the advice from the 10-member Oncologic Drug Advisory Committee (ODAC) – which included Children’s National Health System’s Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology and Director of the Program for Cell Enhancement and Technologies for Immunotherapy – CTL019 will become the first gene therapy to hit the market.

“Many of these children with recurrent cancer are out of other options to treat their illness,” said Dr. Bollard. “We are encouraged by these findings and the potential for this therapy to improve outcomes and quality of life.”

CTL019 is a chimeric antigen receptor (CAR) T-cell therapy, comprised of genetically modified T cells that target CD19, an antigen expressed on the surface of B cells. Also known as tisagenlecleucel, the therapy targets a single type of cancer called acute lymphoblastic leukemia and was created by Novartis.

In clinical trials, CTL019 showed unparalleled effectiveness. Of the 68 patients who received the drug, 52 responded almost immediately, and their cancer disappeared within the first three months. Seventy-five percent of those patients remained cancer-free six months after treatment. The therapy has one main side effect: an immune reaction called cytokine release syndrome, which can be deadly, with extended spiking fevers and other symptoms.

However, because of CTL019’s high efficacy, FDA scientists asked the ODAC panel to focus on the therapy’s safety and manufacturing challenges rather than whether or not it works.

Several committee members, including Dr. Bollard, expressed apprehension about the T-cell subpopulations’ heterogeneity, which could affect safety and efficacy. Another issue for consideration by the ODAC panel was the long-term side effects of CTL019 and the possibility that the T-cell modification could go awry, causing secondary cancers in the future.

Despite these concerns, the committee concluded that the strong efficacy data and the near-term benefits of CAR-T therapy more than tipped the scales in favor of the therapy. ODAC members were also pleased with Novartis’ plan to minimize risk, which includes limiting CTL019 distribution to selected centers with CAR T-cell therapy experience, and extensive, long-term post-marketing surveillance plans.

The FDA is not required to follow the ODAC panel’s advice when making its final decision, but it often does so. A final decision by the FDA is anticipated by late September.

Read more about the story in the Philadelphia Inquirer, Medpage Today and Healio.com.