Adoptive cell therapy: Honing that killer instinct

Humphries, Courtney

doi:10.1038/504s13a

Cited by 47 publications

(38 citation statements)

References 5 publications

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“…One example is passive immunization, or adoptive cell therapy (ACT), which involves the transfusion of autologous or allogeneic T cells into a patient [7]. A variety of ACT methods are under investigation and the most developed of these is termed tumor-infiltrating lymphocyte (TIL) therapy [8]. Tumor-specific T cells are harvested from a biopsy specimen and cultured in vitro in the presence of interleukin (IL)-2 to promote growth.…”

Section: Introductionmentioning

confidence: 99%

MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside

Wittig¹,

Schmidt

Scheithauer³

et al. 2015

Critical Reviews in Oncology/Hematology

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The adaptive immune system has been the main focus of immunological strategies in oncology with only more recent approaches targeting innate immunity. Endosomal toll-like receptors (TLR-7, TLR-9) activate innate immune responses by signaling damage-associated molecular patterns (DAMP) from decaying tumor cells. This has led to the development of DNA-based TLR-9 agonists, which induce antitumor activity through innate and subsequent adaptive immune responses. Early clinical trials with CpG-ODN as TLR-9 agonists were associated with unfavorable tolerability and narrow clinical efficacy, leading to failure in pivotal trials. dSLIM, the active ingredient of MGN1703, is a DNA-based, radically different molecular alternative to CpG-ODN, which results in genuine antitumor immunomodulation. Preclinical and clinical studies of MGN1703 have confirmed that this TLR-9 agonist has therapeutic potential in a variety of solid tumors, while long-term treatment with high doses was very well tolerated. A pivotal trial of first-line maintenance treatment with MGN1703 in patients with metastatic colorectal cancer is underway.

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Section: Introductionmentioning

confidence: 99%

MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside

Wittig¹,

Schmidt

Scheithauer³

et al. 2015

Critical Reviews in Oncology/Hematology

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“…These T cells are then infused into the patient in an attempt to boost the immune response against the tumor [152] . Autologous or allogeneic ex vivo expanded NK cells is an example of ACT.…”

Section: Adoptive Cell Therapymentioning

confidence: 99%

Immunobiology of hepatocarcinogenesis: Ways to go or almost there?

Patel

Schutzer

Pyrsopoulos

2016

WJGP

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“…Along similar lines, it is difficult to identify a therapeutic paradigm that attracts considerably more attention than others, with the obvious exceptions of immunomodulatory mAbs employed as standalone immunotherapeutic interventions (58 studies). Thus, immunomodulatory mAbs are currently being tested in combination with a wide panel of chemo-, radio-, and immunotherapeutic regimens, including (but not limited to): (1) conventional and immunogenic chemotherapeutics (7 studies), [217][218][219][220][221][222] (2) targeted anticancer agents (19 studies), 223,224 (3) radiation therapy, in one of its variants (6 studies), 225,226 (4) hormone therapy (1 study), [227][228][229] (5) [241][242][243][244][245][246][247][248] (9) Toll-like receptor (TLR) agonists (1 study), 249,250 (10) adoptive cell transfer (3 studies), 236,237,[251][252][253] (11) oncolytic virotherapy (2 studies), 70,254-256 (12) indoleamine 2,3-dioxygenase 1 (IDO1)-targeting strategies (3 studies), 257 (13) so-called immunomodulatory drugs, i.e., thalidomide, lenalidomide or pomalidomide (3 studies), 258 and (14) immunomodulatory mAbs with a distinct mechanism of action (17 studies) 259 ( Table 2). Of note, all these studies are active (NCT status: "Active, not recruiting," "Not yet recruiting" or "Recruiting"), with 4 notable exceptions.…”

Section: Update On the Development Of Immunomodulatory Monoclonal Antmentioning

confidence: 99%

Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications

Bloy²,

et al. 2015

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These authors contributed equally to this work. Keywords: ipilimumab, MEDI4736, MPDL3280A, nivolumab, pembrolizumab, urelumab Abbreviations: CRC, colorectal carcinoma; CTLA4, cytotoxic T lymphocyte-associated protein 4; FDA, Food and Drug Administration; IL, interleukin; KIR, killer cell immunoglobulin-like receptor; mAb, monoclonal antibody; NK, natural killer; NSCLC, nonsmall cell lung carcinoma; PD-1, programmed cell death 1; RCC, renal cell carcinoma; TGFb1, transforming growth factor b1; TLR, Toll-like receptor; TNFRSF, tumor necrosis factor receptor superfamily; Treg, regulatory T cellImmunomodulatory monoclonal antibodies (mAbs) differ from their tumor-targeting counterparts because they exert therapeutic effects by directly interacting with soluble or (most often) cellular components of the immune system. Besides holding promise for the treatment of autoimmune and inflammatory disorders, immunomodulatory mAbs have recently been shown to constitute a potent therapeutic weapon against neoplastic conditions. One class of immunomodulatory mAbs operates by inhibiting safeguard systems that are frequently harnessed by cancer cells to establish immunological tolerance, the so-called "immune checkpoints." No less than 3 checkpoint-blocking mAbs have been approved worldwide for use in oncological indications, 2 of which during the past 12 months. These molecules not only mediate single-agent clinical activity in patients affected by specific neoplasms, but also significantly boost the efficacy of several anticancer chemo-, radio-or immunotherapies. Here, we summarize recent advances in the development of checkpoint-blocking mAbs, as well as of immunomodulatory mAbs with distinct mechanisms of action.

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Adoptive cell therapy: Honing that killer instinct

Cited by 47 publications

References 5 publications

MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside

MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: From bench to bedside

Immunobiology of hepatocarcinogenesis: Ways to go or almost there?

Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications

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