Tag Archive for: cancer research

Dalia Haydar

Harnessing children’s immune systems to fight their own brain tumors

Dalia Haydar, Pharm.D., Ph.D., principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies, recently joined Children’s National Hospital to help develop breakthrough treatments that hopefully will be a key in the fight against pediatric brain tumors. She brings her deep experience at St. Jude Children’s Research Hospital to the Center for Cancer and Immunology Research (CCIR) to help support the NexTGen team’s 10-year, $25-million Cancer Grand Challenges award.

Dalia – literally – has drive: She commutes 180 miles round trip from her home in Hershey, Pa., to her lab. She says she is grateful to be at one of the few research institutions in the world that is researching how to harness the power of CAR T-cell therapies to attack solid tumors in kids. While these therapies have been approved to treat leukemia and other blood cancers, solid tumors have proven far more stubborn. Haydar has tremendous hope that she and the team led by CCIR Director Catherine Bollard, M.D., M.B.Ch.B., will change that.

Q: Could you explain the importance of this research?

A: Unfortunately, once a patient is diagnosed with a brain tumor, especially a kid, there’s very little we can do. Using chemotherapy or radiation therapy has big disadvantages because of developmental delays and other side effects. We are hoping this kind of immunotherapy – where we take the patient’s own immune cells and engineer them in the lab to attack their cancer – will eradicate their very harsh and aggressive tumors, without causing significant adverse effects.

Q: How are researchers at Children’s National going to attack solid tumors with a treatment originally designed for blood cancers?

A: We have a lot of resources and expertise at Children’s National that we are trying to put together to develop a therapy that would cure brain tumors. Unfortunately, solid tumors are hard to treat and there are several challenges for any kind of immunotherapy. But right now, being at a place where all the necessary resources, support and expertise are available, we are hoping to address each of these challenges, and we are determined to do something in a meaningful timeframe to push that survival curve toward the advantage of those kids.

Q: How soon can this work be done?

A: Within two or three years, we are hopeful we’ll be able to identify the best working regimen of this CAR T-cell immunotherapy and investigate if it will work in a patient. I foresee, in the next 5 to 10 years, that we’re hopefully going to have such therapy for kids with brain tumors.

Q: What has surprised most you in your work?

A: There are so many challenges in developing immunotherapies for kids with brain tumors. First, if it works for adults, it doesn’t necessarily work for kids. Some of the tumors in kids are more aggressive. We need to understand the tumor itself, besides understanding the immunotherapy we’re developing.

The other challenge is CAR-T immunotherapy is not like a pill or taking radiotherapy that is standardized for several patients. It’s a very expensive therapy. It’s taking the patient’s own immune cell, like a bone marrow transplant. We put it in the lab, re-engineer the cells without transforming them into a cancer cell, enable those immune cells to attack the cancer, and then put them back into the patient. There are a lot of steps you need to take to make sure you don’t artificially harm those cells or introduce contamination.

One of the most intriguing challenges for me is how we make immunotherapy work for kids who have different kinds of brain tumors – a medulloblastoma versus a glioma versus an embryonal tumor. This is one of the challenges that keeps me on my toes, and I’m hoping to answer.

Q: What is the power of being in a multi-center environment like the Children’s National Research Institute?

A: We have to do enough science on the bench to support any proposal for the therapy to move to the clinic. The last thing we want to do is to investigate a drug or therapy in patients without really knowing how it works and the potential adverse effects. Being able to work with researchers at different stages of the bench-to-bedside spectrum, as well as being able to have access to patient samples and innovative preclinical models, helps push the science forward in a shorter time frame.

Cancer cells

Searching for the key to treating neuroblastoma tumors in kids

Cancer cells

Jianhua Yang, Ph.D., has dedicated his research to finding the molecular mechanism of neuroblastoma development and is working to develop novel therapeutics.

There continues to be an urgent need to identify novel therapies for childhood cancers. Neuroblastoma (NB) is the most common malignant solid tumor in children and contributes to more than 15% of all pediatric cancer-related deaths. Despite strides made in chemotherapy treatment over the past 30 years, NB largely remains an incurable disease. That’s why Jianhua Yang, Ph.D., associate professor and research faculty at the Center for Cancer and Immunology Research at Children’s National Hospital, has dedicated his research to finding the molecular mechanism of NB development and is working to develop novel therapeutics to target molecules he and his team identify in the lab.

Q: What has driven you to do this research?

A: In order to design better and potentially more effective NB treatment approaches, we must further understand the mechanism that activates NB development. We don’t know what that mechanism is yet, and that’s what we’re working to unlock. I felt with my training in cell biology and immunology, I could use that background to help develop novel therapies.

The research is hard and can often times feel frustrating. But I feel I’m working on something that has the potential to make a huge difference. I tell the researchers I work with that you have to really believe in what we’re doing. We’re doing something very different. Before I moved to D.C. to join Children’s National, I sent a text to a former mentor to let him know I was joining the team here to continue my work. His reply said, “I’ve always had confidence in you,” and it’s that type of encouragement that drives me to keep going.

Q: What is your current focus in this area?

A: Specifically, we’re working on two targets right now:

  1. To define the role and regulation of CaM kinase-like vesicle-associated (CAMKV) in NB development and examining the therapeutic potential of CAMKV kinase inhibition for treating NB in pre-clinical models. We’ve found that CAMKV is highly expressed in NB tumor samples and its kinase activity is required for tumor growth. So, if we knock out this gene, tumor cells will die. We’re studying how it is being activated, and if we can find out what causes it, we can find a way to inhibit its activation. Targeting CAMKV is a novel concept for treating NB. CAMKV kinase inhibitors may serve not only as stand-alone therapies but also as effective adjuncts to current chemotherapeutic regimens treating this aggressive pediatric malignancy.
  2. To define the role and regulation of transmembrane protein 108 (TMEM108) in NB development and examine the therapeutic potential of TMEM108 functional blockade for treating NB in pre-clinical models. Evolutionarily, in human genome it has no other family member, it’s a loner. And if you knock it out in NB tumor cells, tumor cells will die. We’re learning how it functions through our basic research, which is quite difficult. But we’re thinking if we can find the antibody to bind to it and block its function, we could stop the tumor from growing or even cause the tumor to die.

Q: What excites you about doing this work within the Center for Cancer and Immunology Research?

A: At Children’s National, I’ll be able to combine my work with the incredible work in immunotherapy that Drs. Catherine Bollard and Muller Fabbri are doing. I’m excited to be here to have that strong collaboration with their labs to develop new therapies.

In the next 5 years, I feel we’ll be able to identify good blocking antibodies that we can then test combinations of to see how it blocks tumor growth. If we can find ways to combine that antibody therapy with traditional chemotherapy options, we can achieve a real cure for NB.

Learn more about the Center for Cancer and Immunology Research.

Pediatric research consortia unveil CAVATICA data platform

Javad Nazarian, PhD, MSC, joined peers from prestigious children’s hospitals from around the world.

Dr. Nazarian’s lab at Children’s is part of the CBTTC, which has helped in launching CAVATICA. Pictured (from left to right): Dr. Nazarian, Sabine Mueller, M.D., Ph.D. (PNOC Trial Director), Rishi Lulla, M.D. (CBTTC Executive Director), Francis Collins, M.D., Ph.D., (NIH Director), and Adam Resnick, PHD (CBTTC Scientific Director).

Earlier this week, The White House released the Cancer Moonshot report, which calls upon the public and private sectors to transform cancer research and care. Children’s National’s Javad Nazarian, Ph.D., M.S.C.,  joined peers from prestigious children’s hospitals from around the world at the news conference. Dr. Nazarian is a key player in the initiative, as his lab is part of the Children’s Brain Tumor Tissue Consortium (CBTTC) and is answering the call to action. The CBTTC and the Pacific Pediatric Neuro-Oncology Consortium, in partnership with Seven Bridges, announced the launch of CAVATICA, a data analysis platform that will help researchers to collaboratively access and share data about pediatric cancers, congenital disorders and rare diseases such as epilepsy and autism. More data will be connected than ever before—CAVATICA will interoperate with the Genomic Data Commons and other NIH data repositories. “It’s an exciting time for research,” says Dr. Nazarian.