Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells

Abstract

Purpose: Previously, we showed that adoptive transfer of in vivo vaccine-primed and ex vivo (anti-CD3/anti-CD28) costimulated autologous T cells (ex-T) at day +12 after transplant increased CD4 and CD8 T-cell counts at day +42 and augmented vaccine-specific immune responses in patients with myeloma. Here, we investigated the safety and kinetics of T-cell recovery after infusing ex-Tat day +2 after transplant. Experimental Design: In this phase I/II two-arm clinical trial, 50 patients with myeloma received autografts after high-dose melphalan followed by infusions of ex-T at day +2 after transplant. Patients also received pretransplant and posttransplant immunizations using a pneumococcal conjugate vaccine only (arm B; n = 24) or the pneumococcal conjugate vaccine plus an HLA-A2^restricted multipeptide vaccine for HLA-A2 + patients (arm A; n = 26).

Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination

“…[53][54][55] However, accumulating evidence has demonstrated that prolonged in vitro expansion of T cells can cause a progressive loss of replicative capacity and functional exhaustion limiting their in vivo antitumor efficacy. 19,56 To limit the detrimental impact of prolonged in vitro culture, we used a time-constrained exposure to anti-CD3/anti-CD28 to BLOOD, 27 AUGUST 2009 ⅐ VOLUME 114, NUMBER 9…”

Transfer of influenza vaccine–primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial

“…The apparent difference in CD8 effector memory populations between the primed group and the nonprimed group is not significant and is due to 3 outliers with engraftment syndrome. 30 Therefore, there were no differences in T-cell subsets between the 2 arms.…”

“…The cells were depleted of monocytes and cryopreserved. The T-cell manufacturing process has been described previously 30 and consisted of CD3 and CD28 bead-based stimulation. All infused T-cell products were required to meet safety and release criteria specified by the Food and Drug Administration before infusion.…”

“…30 In this study, we examined functionally distinct T-cell subsets. T-cell recovery differed dramatically between CD4 and CD8 T cells; however, there were no differences between the primed and nonprimed groups.…”

Immunotherapy for B-Cell Neoplasms Using T-Cells Expressing Chimeric Antigen Receptors : From Antigen Choice to Clinical Implementation

“…[11][12][13] It has been reported that the day of adoptive T-cell transfers in relation to preconditioning regimens is critical as T cells given at day two after stem cell transplantation show superior persistence as compared to those given in later days. 14 Until recently, development of this personalised T-cell-based therapy was limited due to the lack of gene transfer techniques and efficient T-cell culture systems. Therefore, previous clinical applications with T cells expressing CAR showed modest clinical activities, as these engineered T cells demonstrated a limited expansion in vivo and rapidly disappeared from circulation.…”