The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Abstract

We performed a Phase I/II clinical trial to study the feasibility, toxicity and efficacy of allogeneic cytokineinduced killer (CIK) cell expansion, and treatment for patients with haematological malignancies who relapsed after allogeneic haemopoietic SCT (allo-HSCT). Allogeneic CIK cells were successfully generated for a total of 24 patients, including those from patients' own leukapheresis products in 5 patients who had no access to further donor cells. The median CD3 þ T-cell expansion was 9.33 (1.3-38.97) fold, and CD3 þ CD56 þ natural killer (NK)-like T-cell expansion was 27.77 (2.59-438.93) fold. A total of 55 infusions were done for 16 patients who had either failed or progressed after initial response to various individualized chemotherapy regimens and donor lymphocyte infusion (DLI), at doses ranging from 10 to 200 million CD3 þ cells/kg. Response attributable to CIK cell infusion was observed in five patients. These included two with ALL, two with Hodgkin's disease (HD) and one with AML, and two of whom had a response sustained for more than 2 years. Acute GVHD occurred in three and was easily treatable. This study provides some evidence suggestive of the efficacy of allogeneic CIK cells even after failure of DLI in some cases.

Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

“…Thus far, CIK cell infusions had only been tested after matched-donor allogeneic transplantation. 4,5,10 Our data demonstrate a similar safety and feasibility of CIK cell therapy from haploidentical donors.…”

“…CIK cells mediate both specific MHC-restricted recognition and non-MHC-restricted cytotoxicity against target cells. [2][3][4][5][6] The activating NK cell receptor, NKG2D, has a crucial role in binding and cytolytic activity of CIK cells against tumor cells expressing the corresponding ligands. 2,3 The best characterized ligands for NKG2D are relatively restricted to tumor cells.…”

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

“…Cellular therapy interventions that might ameliorate the increased GVHD associated with low ALC30 include post-transplant infusions of rapamycin-resistant CD4 T-cells (enriched for regulatory T cells) or NK-cell DLI, both of which have the potential to maintain the GVL effect while limiting aGVHD. [47][48][49] Further studies are needed to define the critical cell phenotype of ALC30 and to better define the mechanism by which high ALC30 protects AHSCT recipients from aGVHD and NRM, thereby improving transplant outcomes. Also adjusted for donor gender, donor CMV status, recipient gender, recipient CMV status, relapse risk, intensity and any blank cells (also NS).…”

Strategies before, during, and after hematopoietic cell transplantation to improve T-cell immune reconstitution

“…These T cells can be expanded ex vivo after stimulation with antigenpresenting cells presenting specific antigens, such as CMV, EpsteinBarr virus, and adenovirus, 110 or against malignant cells to induce GVL. 111 A drawback of this therapy is the long time needed for production of specific T cells. g capture, based on interferon g production, of functional antigen-specific T cells from a donor is a faster alternative.…”