Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes

摘要: Development of a standardized platform for the rapid expansion tumor-infiltrating lymphocytes (TILs) with anti-tumor function from patients limited TIL numbers or tumor tissues challenges their clinical application. To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs) direct and TILs isolated primary cancer specimens. outgrown in IL-2 undergo rapid, CD28-independent response to aAPC stimulation that requires provision exogenous cytokine support. aAPCs induce numerical is statistically similar an established method at 100-fold lower feeder cell ratio, greater than those achievable using anti-CD3/CD28 activation beads extended culture. aAPC-expanded antigen-specific cells, remain amenable secondary aAPC-based expansion, have low CD4/CD8 ratios FOXP3+ CD4+ frequencies. can also be expanded directly fresh enzyme-digested specimens when pulsed aAPCs. These "young" are tumor-reactive, positively skewed CD8+ lymphocyte composition, CD28 CD27 expression, contain fewer T compared parallel cultures. Genetically-enhanced represent standardized, "off-the-shelf" ex vivo suitable number, phenotype use immunotherapy.