Human cell‐based artificial antigen‐presenting cells for cancer immunotherapy

Abstract

Summary Adoptive T-cell therapy, where antitumor T cells are first prepared in vitro, is attractive since it facilitates the delivery of essential signals to selected subsets of antitumor T cells without unfavorable immunoregulatory issues that exist in tumor-bearing hosts. Recent clinical trials have demonstrated that antitumor adoptive T-cell therapy, i.e. infusion of tumor-specific T cells, can induce clinically relevant and sustained responses in patients with advanced cancer. The goal of adoptive cell therapy is to establish antitumor immunological memory, which can result in life-long rejection of tumor cells in patients. To achieve this goal, during the process of in vitro expansion, T-cell grafts used in adoptive T-cell therapy must to be appropriately educated and equipped with the capacity to accomplish multiple, essential tasks. Adoptively transferred T cells must be endowed, prior to infusion, with the ability to efficiently engraft, expand, persist, and traffic to tumor in vivo. As a strategy to consistently generate T-cell grafts with these capabilities, artificial antigen-presenting cells have been developed to deliver the proper signals necessary to T cells to enable optimal adoptive cell therapy.

BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models

“…In were weekly stimulated with aAPC/A2 pulsed with 10 μg/ml heteroclitic MART1 [27][28][29][30][31][32][33][34][35] peptide at an E:T ratio of 10:1 as previously described (53). Synthetic peptides were obtained from ProImmune.…”

“…Cell lines. Both aAPC/mOKT3 and aAPC/A2 are derived from the human erythroleukemic cell line K562 and were established as previously described (30). aAPC/A2 has successfully been used in the clinic (8).…”

“…JQ1-treated DMF5-transduced T cells showed superior proliferation upon serial stimulation by aAPC/A2 pulsed with MART1 [27][28][29][30][31][32][33][34][35] peptide ( Figure 5B). Although no significant difference in the cellular division rate was found, the JQ1-treated T cells showed better viability than the (-)-JQ1-treated T cells upon stimulation ( Figure 5, C and D).…”

T cell engineering as therapy for cancer and HIV: our synthetic future

“…In addition, culture systems that provide costimulation by immobilized ligands on beads have improved the function of adoptively transferred T cells [49]. Sophisticated artificial antigen-presenting cells that provide arrays of selected costimulatory molecules and cytokines have been developed [50,51], as reviewed by Butler & Hirano [52].…”

Engineered cells for costimulatory enhancement combined with IL-21 enhance the generation of PD-1-disrupted CTLs for adoptive immunotherapy

“…Several other groups are currently conducting clinical trials of adoptive cell transfer, utilizing aAPCs derived from K562, thus further confirming the versatility and utility of this cell line. [17]. Receptor 4-1BB (CD137) is a member of the tumor necrosis factor (TNF) receptor superfamily that has T-cell costimulatory functions [18].…”