Transient stimulation expands superior antitumor T cells for adoptive therapy

Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy

“…This situation can be further exacerbated by conventional ex vivo cell manufacturing processes (19,20,57,58). We therefore next asked whether AKTi preserves key markers of cellular differentiation and effector function relative to an unstimulated starting population of T cells.…”

“…Thus, relatively differentiated T cell products are generated using many current clinical manufacturing methods for genetically engineered T cells because these methods focus primarily on the generation of large numbers of antitumor cells (19,20). This is especially true in heavily pretreated patients who have starting apheresis populations containing a paucity of naive/ early memory T cells (21)(22)(23).…”

Toward precision manufacturing of immunogene T-cell therapies

“…More recently, K562 cells engineered to express a membrane-bound form of anti-CD3 monoclonal antibody (mAb) (mOKT3) and additional co-stimulatory molecules (CD80 and CD83) were shown to induce robust T-cell activation [69,70].…”

“…In a comparative analysis with anti-CD3/CD28 Dynabeads, K562-expressing mOKT3 (K562/ mOKT3) provided a relatively transient stimulation of T cells and generated superior proliferative signals for CD8+ T cells, accompanied by the enrichment of the Tscm subset [69]. This resulted in prolonged persistence and anti-tumor efficacy of these adoptively transferred T cells in vivo [69].…”

“…This resulted in prolonged persistence and anti-tumor efficacy of these adoptively transferred T cells in vivo [69].…”