Autologous Cytokine-Induced Killer Cells as Post-Transplant Cellular Immunotherapy.
Authors: Arai Sally , Sheehan Kevin , Moore Sherry , Laport Ginna , Johnston Laura , Lowsky Robert , Miklos David , Goldstein Keith , Weng Wen-Kai , Shizuru Judith , Horning Sandra , Negrin Robert 
Published: October 2019

Disease relapse remains a major cause of treatment failure following autologous hematopoietic cell transplantation (HCT) for patients with high-risk malignancies. Cellular immunotherapy using activated autologous effector cells to recognize and kill tumor targets in a minimal disease state after transplant is a novel strategy to reduce relapse and improve survival. In this phase I/II study, we investigated the safety and efficacy of administering ex-vivo expanded autologous cytokine-induced killer (CIK) cells as post-transplant cellular immunotherapy. Patients with high risk recurrent or refractory Hodgkin’s disease (HD)- defined as B symptoms at relapse, pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation- and patients with multiple myeloma (MM) and acute myelogenous leukemia undergoing single autologous HCT were eligible. The autologous CIK cells were ex-vivo expanded from an aliquot of the patient’s autologous apheresis product for 21–28 days in the presence of IFN-γ, IL-2, and OKT-3 to a maximal cell dose of 2×108 CIK cells/kg. The CIK cell population is uniquely characterized by having the functional and phenotypic properties of both T cells and NK cells, (i.e. expressing CD3 and CD56 molecules) and kills tumor targets through an NKG2D-mediated mechanism. A single infusion of CIK cells was given on day 42–63 following autologous transplantation. Monitoring for infusion-related toxicities was performed for the first 28 days. Disease response assessments were done at day 90, 180, one year and annually. Correlative studies on cytokine profile, primary tumor cytotoxicity and NKG2D ligand expression are being performed. Thirteen patients (ages 19–64) have received autologous CIK cell infusions to date. Nine patients have high risk HD; four patients have MM with a single autologous HCT. The median CIK cell dose for infusion was 0.9×108 cells/kg (range 0.2–2×108/kg). The only infusional toxicities observed have been one grade 1 headache and one grade 1 nausea- both were transient and resolved. Hematologic parameters have not been affected by the infusion. In vitro cytotoxicity of cultured CIK cells was assessed against a panel of leukemia and lymphoma cell lines including Jurkat, DB, OCI-Ly8 and SUDHL4. Median 51-Cr release at 40:1 (E:T) ranged from 71% killing against Jurkat cells to 21% against DB. The first patient on the trial with high risk HD involving the lung and bone marrow is one year from HCT without evidence of disease relapse. Four other patients (all high risk HD) have completed day 180 disease response assessments and have no evidence of disease relapse. One HD patient had progressive disease at day 100. The three evaluable MM patients have no disease progression at day 90–180. In this first phase of study, we have confirmed the safety of administering autologous CIK cells at a single maximal dose at day 42–63 post-transplant. Maintenance of disease response in these high risk patients is encouraging in the first year following transplantation.