Cellular immunotherapy strategies for Ewing sarcoma

Abstract

Ewing sarcoma is a rare cancer of bone and soft tissues defined by a specific chromosomal rearrangement. Preclinical development of immunological treatment strategies includes expansion of T cells with native or grafted T-cell receptor specificities for Ewing sarcoma-associated intracellular antigens, and T-cell engineering with chimeric antigen receptors targeting surface antigens. In vitro preactivated NK cells may also have activity in this cancer. Major challenges are the heterogeneity of antigen expression in individual Ewing sarcomas, and the coexpression of most candidate targets on normal cells. Moreover, homing of therapeutic effector cells to both primary and metastatic tumor sites and adequate function within the immunosuppressive tumor microenvironment will have to be ensured to allow for effective immune targeting of this cancer.

Keywords: Ewing sarcoma; NK cell; T-cell receptor; T-cell therapy; chimeric antigen receptor; regulatory T cell; tumor antigen; tumor immune escape; tumor microenvironment.