Are there side effects with CAR-T cells?
CAR-T cells are not free from non-targeted and unintended effects. The common usage of viral vector systems for gene transfer carries a chance of insertional mutagenesis. CAR integration into more differentiated cells (as opposed to stem cells) can potentially limit this.1
Since very few antigens are tumor cell-exclusive, CAR antigen targeting can result in the targeting and elimination of healthy cells. This is most prominent when CAR-T cells are used to treat hematopoietic cancers (e.g., CD19 targeting will eliminate all CD19 B cells, resulting in B-cell aplasia), but can also manifest as “off organ” toxicities – where a highly expressed cancer cell antigen in one organ is also a key mediator of physiological function in a different organ.1
Finally, the rapid and sudden introduction of a large number of active and potent T cells has a dramatic effect on the extent and nature of host immune responses. Systemic inflammation- and cytokine storm-related toxicity has been observed post CAR-T cell administration.1
Reference:
1. G. Dotti, et al., “Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T cells,” Immunol Rev 257(1):10, 2014.
Since very few antigens are tumor cell-exclusive, CAR antigen targeting can result in the targeting and elimination of healthy cells. This is most prominent when CAR-T cells are used to treat hematopoietic cancers (e.g., CD19 targeting will eliminate all CD19 B cells, resulting in B-cell aplasia), but can also manifest as “off organ” toxicities – where a highly expressed cancer cell antigen in one organ is also a key mediator of physiological function in a different organ.1
Finally, the rapid and sudden introduction of a large number of active and potent T cells has a dramatic effect on the extent and nature of host immune responses. Systemic inflammation- and cytokine storm-related toxicity has been observed post CAR-T cell administration.1
Reference:
1. G. Dotti, et al., “Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T cells,” Immunol Rev 257(1):10, 2014.
