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Project Update Summaries 2014

Phase I Clinical Trial - 3rd Generation Genetically Modified Autologous T-cell Therapy


The RTF partnered with Solving Kids' Cancer on an immunotherapy clinical trial using children's own immune cells that are re-engineered to become cancer-killing T-cells (T-cell CARs) targeting specific markers on neuroblastoma cells called GD2. A similar technology was recently first used in children with relapsed leukemia and has been a real breakthrough - over 50% complete responses in 1 1/2 years. We are hopeful that T-cells CARs for solid tumors like neuroblastoma will be just as successful as the early results in blood cancers. This is a first-in-children study with a goal to enroll 14 children and complete in early 2015.

This T-cell neuroblastoma trial recently opened at Texas Children's Cancer Center/Baylor School of Medicine, much to the excitement of families who desperately need innovative treatment options. We are also excited to have supported the development of this new cutting-edge therapy that introduces a new category of treatment that has the potential to be more effective and less toxic than chemotherapy, radiation and targeted drugs.

Baylor T-cell Clinical Trial & CHOP Mosse ALK Antibody Development Program

Ph I T-cell GD2 CAR for neuroblastoma (Baylor)

To date, 14 patients have been consented for procurement and 2 patients have been treated on Dose Level 1. We are currently within the 6 week waiting period prior required by the FDA prior to proceeding with Dose Level 2.

Our first patient continues to have detectable T-cell CARs within his peripheral blood samples. The number of cells was stable through week 4 and then decreased significantly at the week 6 evaluation. He had clinical improvement, but unfortunately had progression of disease on imaging. Our second patient is due for his disease re-evaluation in 2 weeks. The 3rd patient is set to enroll this week at the next dose level.

Based on data obtained from other T cell studies being conducted at CAGT, we plan to change our T cell manufacturing process from using IL-2 to another cytokine profile. The amendment to the FDA will be submitted on 2/3/14. In addition, we are considering the option of providing fresh cells (as compared to our current frozen product) for those in whom the timing may work.

ALK Monoclonal Antibody Development for neuroblastoma

The central aim in this project is to develop antibodies against the ALK extracellular region that can be used alone or in combination with small molecule ALK kinase inhibitors to block ALK as an oncogenic driver in neuroblastoma.

CHOP's studies in the first project period have yielded a range of antibodies on which to work for Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) applications, as well as avenues for combining agents to identify useful inhibitory approaches.

The inhibitory antibodies have not shown effects against mutated ALK to date – but the fact that binding is retained indicates that these would still be useful for ADCC. Meanwhile, CHOP has set up the pipeline in this first year of study to screen rapidly through additional antibodies for those that do have robust inhibitory effects on mutated ALK.


  • With our commercial collaborator Kollatan, we identified 32 monoclonal antibodies against both the C-terminal and the N-terminal portions of the ALK receptor.
  • Based on the binding affinity we selected the top 12 for further characterization of neuroblastoma cell growth inhibition in vitro. All the initial cell-binding studies were performed in NB1 cells, which express high levels of native ALK.
  • In addition we determined the ability of mABs to bind ALK at the surface of cultured cells. Cellular surface staining showed that both mABs tested (strongest agonist (8H8) and antagonists (8D4) antibodies) bound to ALK. We identified subsets of ALK antibodies that can inhibit (antagonists) and activate (agonists) ALK when overexpressed as a result of gene amplification in the NB1 neuroblastoma cell line.
  • Upon completion of the binding affinity studies, we next wanted to extend the results obtained in NB1 cells to other five neuroblastoma cell lines: NBSD, SY5Y, EBC1, Kelly and NB1643, some of which harbor ALK mutations.
  • These data – together with the results outlined above – illustrate that we now have a collection of antibodies that bind strongly to the ALK extracellular region as purified protein and when expressed on the cell surface as intact receptor. This was a key goal of the first year of this project. These studies have set the stage for our now-ongoing work to identify ALK antibodies that have characteristics that will be useful therapeutically.

About the Foundation

The Ronan Thompson Foundation is a non-profit 501(c)3 organization dedicated to finding a cure for neuroblastoma, a form of childhood cancer. We are currently fundraising to create a world-class neuroblastoma research and care center dedicated to funding both traditional and non-traditional treatments to reduce the number of children affected by this disease and increase survival rates.

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