THE GOLDSMITH LAB
Exploring Novel Therapies for Pediatric Solid Tumors
Kelly C. Goldsmith, MD
RESEARCH
We study the aggressive pediatric solid tumor, neuroblastoma (ps, It's NOT a brain tumor!), bringing novel targeted therapeutics and immunotherapies from bench to bedside. We also perform correlative studies for clinical trials to then determine biomarkers of respose to novel therapies.
Gamma Delta (γδ) T Cell Therapy for Pediatric Solid Tumors
Expanded healthy donor γδ T cells have emerged as a tractable cell therapy candidate for cancer treatment. In collaboration with Drs. Trent Spencer and Chris Doering, our NIH funded preclinical work showed that ex vivo expanded healthy donor γδ T cells potently kill neuroblastoma tumor xenografts in mice when given in combination with anti-GD2 antibody and chemotherapy. Our work recently translated into a FIRST IN HUMAN phase I trial of allogeneic γδ T cells + dinutuximab, irinotecan, temozolomide and zoledronate for patients with relapsed neuroblastoma (NCT05400603) for which Dr. Goldsmith is chair.
Exploring the tumor cell surfaceome for novel immunotherapy targets for neuroblastoma
In collaboration with the lab of Runghu Wu at Georgia Tech, we performing high throughput cell surface proteome profiling of post chemotherapy neuroblastoma xenografts and identified PTK7 to be abundantly expressed on the surface of NBL cells. PTK7 had low to no cell surface expression on normal pediatric tissues and is expressed in a large number of other pediatric cancer types. We found that PTK7 CAR αβ T cells potently killed metastatic neuroblastoma models in mice. We are now working on novel antibody and cell therapies targeting PTK7 in neuroblastoma and other pediatric tumors.
Understanding Biology Behind Disparities in Outcome to Targeted Immunotherapy
Neuroblastoma patients with reported household income poverty who were enrolled and treated with GD2 immunotherapy on a Children's Oncology Group (COG) trial had worse survival compared to patients without reported household income poverty, yet the biologic basis of this difference is not understood (Bona, et al, JCO 2022). Through an R01 funded project, we are performing high throughput genomic/proteomic analysis of tumor and blood from newly diagnosed high risk neuroblastoma patients enrolled on the new COG phase III trial that gives GD2 chemoimmunotherapy upfront (ANBL2131) to determine biomarkers of response. Biomarker results will be correlated to patient outcomes, genomic ancestry testing, and results from a clinical trial-embedded health equity survey (Collaboration with Dr. Kavita Dhodapkar (CHOA), Dr. Kira Bona (Harvard) and Dr. Arlene Naranjo (UF).
Creating a 3D Model of the Neuroblastoma Microenvironment
In collaboration with the Serpooshin
In collaboration with Dr. Vahid Serpooshan, we have been working to create a 3D bioprinted n vitro model of the neuroblastoma tumor microenvironment in order to explore, in a high throughput way, novel immunotherapies by taking into account the cellular and structural barriers faced by these types of therapies. We continue to optimize this model (version 2.0 underway) to include immune cells and matched patient PDXs in order to dissect the individual roles of the NBL TME on antibody and cellular therapy responses.
