Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment. Here, we investigated the effects of B-cell therapy in the SOD1G93A mouse preclinical model of ALS and in a person living with ALS. Purified splenic mature naïve B cells from haploidentical donor mice were administered intravenously in SOD1G93A mice for a total of 10 weekly doses. For the clinical study in a person with advanced ALS, IgA gammopathy of unclear significance, and B lymphopenia, CD19+ B cells were positively selected from a healthy haploidentical donor and infused intravenously twice, at a 60-day interval. Repeated intravenous B-cell administration was safe and significantly delayed disease onset, extended survival, reduced cellular apoptosis, and decreased astrogliosis in SOD1G93A mice. Repeated B-cell infusion in a person with ALS was safe and did not appear to generate a clinically evident inflammatory response. An improvement of 5 points on the ALSFRS-R scale was observed after the first infusion. Levels of inflammatory markers showed persistent reduction post-infusion. This represents a first demonstration of the efficacy of haploidentical B-cell infusion in the SOD1G93A mouse and the safety and feasibility of using purified haploidentical B lymphocytes as a cell-based therapeutic strategy for a person with ALS.

Development and implementation of a computerized system for collection, processing, and administration of cellular therapy products.

Great strides have been made in computerization of ordering processes for general medications and chemotherapy agents. However, systems for ordering, processing, and administration of cellular therapies continue to be largely paper-based, without the safety features of computerized order entry. To address this deficit, Partners Healthcare System Information Services (PHS-IS; Boston, MA) has worked with oncologists and staff in the cell processing laboratory at the Dana-Farber Cancer Institute (Boston, MA) to develop and implement a novel, comprehensive computerized system for physician ordering and management of cellular products. A multidisciplinary team was formed to accomplish the task of developing a cellular product management system. This team identified the unique characteristics of cellular therapies and sought to develop a comprehensive computerized system that addressed these needs. The biotherapy order entry system developed and implemented by PHS-IS includes a suite of three interrelated applications that addresses all requirements of a traditional computerized provider order entry system, as well as features unique to cellular therapies. The biotherapy suite of applications has addressed patient safety concerns, streamlined the ordering of cellular therapy products, and has reduced opportunities for error and delay in product administration.