Cellular Therapy for Children with Central Nervous System Tumors: Mining and Mapping the Correlative Data.

Publication Year:

2023

Authors:

Erin E Crotty, Ashley L Wilson, Tom Davidson, Sophia Tahiri, Juliane Gust, Andrea M Griesinger, Sujatha Venkataraman, Julie R Park, Sabine Mueller, Brian R Rood, Eugene I Hwang, Leo D Wang, Nicholas A Vitanza

PubMed ID:

37160547

Funding Grants:

Phase I Study of IL13Rα2-Targeting CAR T Cells After Lymphodepletion for Children with Refractory or Recurrent Malignant Brain Tumors
The City of Hope Alpha Clinic: A roadmap for equitable and inclusive access to regenerative medicine therapies for all Californians

Public Summary:

Studies conducted in conjunction with clinical trials (correlative studies) are designed to shed light on the biology underlying the intervention and lead researchers to improving patient outcomes. In pediatric cellular immunotherapy trials, correlative studies enable deeper understanding of how T cells act to boost the immune system and facilitate anticancer responses. Here, we review the correlative science in cellular immunotherapy for childhood central nervous system (CNS) tumors, with a focus on T cell therapies. We highlight challenges for aligning correlative data across different trials and offer practical considerations for standardizing approaches to biospecimen collection and data analysis, focusing on preliminary successes.

Scientific Abstract:

PURPOSE OF REVIEW: Correlative studies should leverage clinical trial frameworks to conduct biospecimen analyses that provide insight into the bioactivity of the intervention and facilitate iteration toward future trials that further improve patient outcomes. In pediatric cellular immunotherapy trials, correlative studies enable deeper understanding of T cell mobilization, durability of immune activation, patterns of toxicity, and early detection of treatment response. Here, we review the correlative science in adoptive cell therapy (ACT) for childhood central nervous system (CNS) tumors, with a focus on existing chimeric antigen receptor (CAR) and T cell receptor (TCR)-expressing T cell therapies. RECENT FINDINGS: We highlight long-standing and more recently understood challenges for effective alignment of correlative data and offer practical considerations for current and future approaches to multi-omic analysis of serial tumor, serum, and cerebrospinal fluid (CSF) biospecimens. We highlight the preliminary success in collecting serial cytokine and proteomics from patients with CNS tumors on ACT clinical trials.