Systemic Intravenous Adoptive Transfer of Autologous Lymphokine-activated αβ T-Cells Improves Temozolomide-induced Lymphopenia in Patients with Glioma

Kanemura Y1,2, Sumida M3, Okita Y2, Yoshioka E4, Yamamoto A4, Kanematsu D3, Handa Y3, Fukusumi H4, Inazawa Y3, Takada AI3, Nonaka M2,5, Nakajima S2, Mori K6,7, Goto S8, Kamigaki T8, Shofuda T4, Moriuchi S2,9, Yamasaki M2,10.

Anticancer Res. 2017 Jul;37(7):3921-3932.

Abstract

In this clinical study, we investigated the safety and clinical usefulness of systemic adoptive immunotherapy using autologouslymphokine-activated αβ T-cells (αβ T-cells), combined with standard therapies, in patients with malignant brain tumors. Twenty-three patients with different malignant brain tumors, consisting of 14 treated with temozolomide (TMZ group) and 9 treated without temozolomide (non-TMZ group), received systemic intravenous injections of αβ T-cells (mean=10.4 injections/patient for the TMZ group, and 4.78 for the non-TMZ group). No significant adverse effects associated with the αβ T-cell injection were observed, and the total lymphocyte count (TLC) improved significantly in the TMZ group after five injections. Furthermore, CD8-positive or T-cell receptor V gamma -positive cells were increased with TLC in three patients with glioblastoma multiforme. These findings suggest that systemicαβ T-cell immunotherapy is well tolerated, and may help restore an impaired and imbalanced T-cell immune status, and temozolomide- and/or radiotherapy-induced lymphopenia. Future prospective study is needed to clarify the clinical merits of this immunotherapy.

KEYWORDS:

Glioma; immunotherapy; lymphokine-activated αβ T-cells; lymphopenia; temozolomide