Abstract: Disclosed herein are methods and compositions for determining and improving the likelihood of response and/or determining and decreasing the likelihood of toxicity to a cellular therapy using metabolomics. Embodiments of the disclosure include methods for measuring certain metabolites in biological samples of an individual for determining whether the individual has a responder or non-responder phenotype to the cellular therapy or to a toxicity of the cellular therapy. Embodiments also include compositions for increasing the response to a cellular therapy or decreasing toxicities associated with a cellular therapy. Embodiments also show that plasma metabolomics correlate with efficacy and toxicities associated with CAR-T therapy towards a cancer. The present disclosure relates to compositions and methods for predicting a subject's response to a CAR T-cell therapy, by analyzing the plasma metabolomics of the subject.

Abstract: The current disclosure provides methods and compositions related to treating or preventing neutropenic fever (e.g., cancer therapy-induced neutropenic fever) and/or GVHD (e.g., HCT-related and/or neutropenic fever therapy-induced GVHD). In specific cases, it may be determined whether or not the subject is likely to develop or is at risk of developing neutropenic fever and/or GVHD, such as cancer therapy-induced neutropenic fever and/or HCT-related and/or neutropenic fever therapy-induced GVHD, based on the subject's gut microbiome.

Abstract: The present disclosure concerns methods and compositions related to adoptive cell therapy and its efficacy related to the gut microbiome. In specific cases, it may be determined for an individual whether or not a chimeric antigen receptor (CAR) T-cell therapy will be effective for an individual based on their gut microbiome. An individual may be provided a composition comprising one or more particular microbe compositions based on analysis of the gut microbiome of the individual and prior to administration of CAR T-cell therapy, in specific embodiments.