By introducing the anti-myeloma idiotype (Id)–keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulation T cells, researchers anticipated combining adaptively transferred autologous T cells with a cancer vaccination method would improve therapeutic effectiveness. Patients in the randomized phase 2 experiment received either a control (KLH alone) or an Id-KLH vaccination, autologous transplantation, vaccine-specific costimulation T cells grown ex vivo, and two booster doses of the assigned vaccine.
No dose-limiting toxicity was seen in 36 patients (KLH, n=20; Id-KLH, n=16). At the time of the final evaluation, 6 (30%) and 8 (50%) patients in the KLH-only and Id-KLH groups, respectively, had achieved full remission (P =0.22), and there was no difference in 3-year progression-free survival (59 % and 56 %, respectively; P =0.32). In a 594 Nanostring nCounter gene panel examined for immunological reconstitution (IR), patients receiving Id-KLH had a higher change in IR genes in T cells than those receiving KLH alone. Upregulation of genes related to activation, effector function induction, and memory CD8+ T-cell production was seen following Id-KLH immunization but not after KLH control vaccination. Similarly, the elevation of genes linked with T-cell activation was observed in responding patients. At the outset, all patients showed higher CD8+ T-cell exhaustion markers. In a subgroup of patients receiving Id-KLH, the alterations were linked with functional Id-specific immune responses.
In conclusion, they found much more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm of the combined immunotherapy strategy, indicating the need for additional research into vaccination and adoptive immunotherapy techniques.
