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Innovative Clinical Perspectives for CIK Cells in Cancer Patients.

ABSTRACT: Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in vitro, following extensive manipulation by Interferon gamma (IFN-?), OKT3 and Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell-surface markers. CIK cells have a dual "nature", due to the presence of functional TCR as well as NK molecules, even if the antitumoral activity can be traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In addition to antineoplastic activity in vitro and in several in-vivo models, CIK cells show very limited, if any, GvHD toxicity as well as a strong intratumoral homing. For all such reasons, CIK cells have been proposed and tested in many clinical trials in cancer patients both in autologous and allogeneic combinations, up to haploidentical mismatching. Indeed, genetic modification of CIK cells as well as the possibility of combining them with specific monoclonal antibodies will further expand the possibility of their clinical utilization.

SUBMITTER: Introna M

PROVIDER: S-EPMC5855580 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Innovative Clinical Perspectives for CIK Cells in Cancer Patients.

Introna Martino M Correnti Fabio F

International journal of molecular sciences 20180125 2

Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in vitro, following extensive manipulation by Interferon gamma (IFN-γ), OKT3 and Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell-surface markers. CIK cells have a dual "nature", due to the presence of functional TCR as well as NK molecules, even if the antitumoral activity can be traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In addition to antineoplastic activ ...[more]

PMID: 29370095

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Project description:Cytokine-induced killer (CIK) cells are an immunotherapeutic approach to combat relapse following allogeneic hematopoietic stem cell transplantation (HSCT) in acute leukemia or myelodysplastic syndrome (MDS) patients. Prompt and sequential administration of escalating cell doses improves the efficacy of CIK cell therapy without exacerbating graft vs. host disease (GVHD). This study addresses manufacturing-related issues and aimed to develop a time-, personal- and cost-saving good manufacturing process (GMP)-compliant protocol for the generation of ready-for-use therapeutic CIK cell doses starting from one unstimulated donor-derived peripheral blood (PB) or leukocytapheresis (LP) products. Culture medium with or without the addition of either AB serum, fresh frozen plasma (FFP) or platelet lysate (PL) was used for culture. Fresh and cryopreserved CIK cells were compared regarding expansion rate, viability, phenotype, and ability to inhibit leukemia growth. Cell numbers increased by a median factor of 10-fold in the presence of FFP, PL, or AB serum, whereas cultivation in FFP/PL-free or AB serum-free medium failed to promote adequate CIK cell proliferation (p < 0.01) needed to provide clinical doses of 1 × 106 T cells/kG, 5 × 106 T cells/kG, 1 × 107 T cells/kG, and 1 × 108 T cells/kG recipient body weight. CIK cells consisting of T cells, T- natural killer (T-NK) cells and a minor fraction of NK cells were not significantly modified by different medium supplements. Moreover, neither cytotoxic potential against leukemic THP-1 cells nor cell activation shown by CD25 expression were significantly influenced. Moreover, overnight and long-term cryopreservation had no significant effect on the composition of CIK cells, their phenotype or cytotoxic potential. A viability of almost 93% (range: 89-96) and 89.3% (range: 84-94) was obtained after freeze-thawing procedure and long-term storage, respectively, whereas viability was 96% (range: 90-97) in fresh CIK cells. Altogether, GMP-complaint CIK cell generation from an unstimulated donor-derived PB or LP products was feasible. Introducing FFP, which is easily accessible, into CIK cell cultures was time- and cost-saving without loss of viability and potency in a 10-12 day batch culture. The feasibility of cryopreservation enabled storage and delivery of sequential highly effective ready-for-use CIK cell doses and therefore reduced the number of manufacturing cycles.

Project description:Over the past decade, there has been a growing development of innovative technologies to treat cancer. Many of these technologies are expensive and not funded by health funds. The present study examined physicians' perceptions of the ethical and clinical aspects of the recommendation and use of unfunded technologies for cancer treatment. This mixed-methods study surveyed 127 oncologists regarding their perceptions toward using unfunded innovative cancer treatment technologies, followed by in-depth interviews with 16 oncologists. Most respondents believed that patients should be offered all treatment alternatives, regardless of their financial situation. However, 59% indicated that they often face dilemmas regarding recommending new unfunded treatments to patients with financial difficulties and without private health insurance. Over a third (38%) stated that they felt uncomfortable discussing the cost of treatment with patients. A predictive model found that physicians facing patients whose medical condition worsened due to an inability to access new treatments, and who expressed the opinion that physicians can assist in locating funding for patients who cannot afford treatments, were more likely to recommend unfunded innovative therapies to patients (F = 5.22, R2 = 0.15, p < 0.001). Subsequent in-depth interviews revealed four key themes: economic considerations in choosing therapy, patient-physician communication, the public healthcare fund, and discussion of treatment costs. Physicians feel a professional commitment to offer patients the best medical care and a moral duty to discuss costs and minimize patients' financial difficulty. There is a need for careful and balanced use of innovative life-prolonging technologies while putting patients at the center of discourse on this complex and controversial issue. It is essential to develop a psychosocial support program for physicians and patients dealing with ethical and psychosocial dilemmas and to set guidelines for oncologists to conduct a comprehensive and collaborative physician-patient discourse regarding all aspects of treatment.

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Innovative Clinical Perspectives for CIK Cells in Cancer Patients.

Publications

Innovative Clinical Perspectives for CIK Cells in Cancer Patients.

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