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Trial Watch: Adoptively transferred cells for anticancer immunotherapy.

ABSTRACT: Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with the overall aim of enhancing the proliferation, persistence and functionality of infused cells, as well as to ensure their evolution in an immunological permissive local and systemic microenvironment. In addition, isolated lymphocytes can be genetically engineered to endow them with the ability to target a specific tumor-associated antigen (TAA), to increase their lifespan, and/or to reduce their potential toxicity. The infusion of chimeric antigen receptor (CAR)-expressing cytotoxic T lymphocytes redirected against CD19 has shown promising clinical efficacy in patients with B-cell malignancies. Accordingly, the US Food and Drug Administration (FDA) has recently granted 'breakthrough therapy' designation to a CAR-based T-cell therapy (CTL019) for patients with B-cell malignancies. Considerable efforts are now being devoted to the development of efficient ACT-based immunotherapies for non-hematological neoplasms. In this Trial Watch, we summarize recent clinical advances on the use of ACT for oncological indications.

SUBMITTER: Fournier C

PROVIDER: S-EPMC5674950 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Trial Watch: Adoptively transferred cells for anticancer immunotherapy.

Fournier Carole C Martin François F Zitvogel Laurence L Kroemer Guido G Galluzzi Lorenzo L Apetoh Lionel L

Oncoimmunology 20170811 11

Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected ...[more]

PMID: 29147628

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Project description:Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and ?-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients.

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Trial Watch: Adoptively transferred cells for anticancer immunotherapy.

Publications

Trial Watch: Adoptively transferred cells for anticancer immunotherapy.

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