Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC.

Brahmer, Julie R.; Rizvi, Naiyer A.; Lutzky, Jose; Khleif, Samir N.; Blake-Haskins, Andy; Li, Xia; Robbins, Paul B.; Vasselli, Jim; Ibrahim, Ramy; Antonia, Scott

doi:10.1200/jco.2014.32.15_suppl.8021

Cited by 53 publications

(33 citation statements)

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“…87 Several durable remissions were achieved in patients with NSCLC (n=13) and MEDI-4736 had an acceptable safety profile. 88 Expansion cohorts are currently being enrolled for this trial to further test the safety and efficacy of MEDI-4736 in advanced solid tumors, including lung cancer (NCT01693562) ( Table 1).…”

Section: Medi-4736mentioning

confidence: 99%

Immunologic Checkpoint Blockade in Lung Cancer

Reck

Paz‐Ares

2015

Seminars in Oncology

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Section: Medi-4736mentioning

confidence: 99%

Immunologic Checkpoint Blockade in Lung Cancer

Reck

Paz‐Ares

2015

Seminars in Oncology

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“…Immunotherapy through immune checkpoint reactivation of blocking the PD-1/PDL-1 signaling pathway to recover patients' T-cell function has been actively studied recently and shows preliminary, but promising, results, leading to renewed attention and interest in tumor-induced immunosuppression and immunotherapy of renal cell carcinoma and lung cancer, in addition to melanoma. [10][11][12][13][14][15][16] Previous studies demonstrated that iPSC-conditioned medium was associated with enhanced cytotoxic function of T cells and NK cells. [7][8][9] Thus, we hypothesized that iPSC-conditioned medium could restore anticancer immunity through the enhancement of CTL activity and NK cell activity.…”

mentioning

confidence: 99%

Induced Pluripotent Stem Cell–conditioned Medium Suppressed Melanoma Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity

Hsieh

Luo

Chien

et al. 2016

Journal of Immunotherapy

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Induced pluripotent stem cells (iPSCs) can secrete cytokines that are involved in T-cell development and affect cytotoxic activity. To assess the effect of iPSC-conditioned medium on tumorigenicity, we retrieved splenocytes from B6 mice and cocultured them with or without irradiated B16 melanoma cells, mouse interleukin-2 (mIL-2), or iPSC-conditioned medium. Splenocyte cytotoxicity assays against B16 melanoma cells [as cytotoxic T lymphocyte (CTL) activity] and P815 cells [as natural killer (NK) activity] were performed. IL-10 and interferon-γ concentrations were measured. An in vivo subcutaneous B16 melanoma growth model was performed in B6 mice and treated with iPSC-conditioned medium. The lymphocyte subpopulation depletion test was performed to determine effectors against B16 melanoma cells. We found that unstimulated splenocytes had little cytotoxic activity. Without tumor cells, mIL-2 could augment iPSC-conditioned medium-treated CTL and NK activities (P<0.01). With irradiated tumor cells, mIL-2 treatment of splenocytes could not enhance CTL or NK activity, but iPSC-conditioned medium could enhance CTL and NK activity (P<0.001). Irradiated tumor cells induced mice splenocytes to secrete more IL-10, similar to mIL-2 treatment, but not iPSC-conditioned medium treatment. mIL-2 had better efficacy than conditioned medium in inducing splenocyte interferon-γ production. The CTL and NK cell depletion test showed that the immunostimulating effect of iPSC-conditioned medium on splenocytes was through the enhancement of NK cellular activity (P<0.05). The subcutaneous melanoma growth model showed that B16-bearing mice treated with an iPSC-conditioned medium intraperitoneal injection had a decreased tumor growth rate (P<0.01). Our study suggests that iPSC-conditioned medium had a protective effect against tumor-induced immunosuppression through the enhancement of host NK cellular activity.

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“…In the group treated with 10 mg/kg Q2W, RR was 13 % overall (39 and 5 % in PD-L1-positive and PD-L1-negative tumors, respectively) [35]. As seems to be the case with other anti-PD-L1 agents, in contrast to anti-PD-1 antibodies, no grade ≥3 pneumonitis was observed.…”

Section: Docetaxel As Standard Second-line Chemotherapymentioning

confidence: 80%

Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer

Zimmermann

Peters

2015

Cancer Metastasis Rev

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The development of novel effective immunotherapeutic agents and early clinical data hinting at significant activity in non-small cell lung cancer (NSCLC) has introduced yet another player in the field of management of advanced disease. At present, first-line cytotoxic chemotherapy is generally withheld pending results of molecular testing for any actionable genetic alteration that could lead to targeted treatment, and in their absence chemotherapy is prescribed as a default therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors with standard platinum-based doublet chemotherapy are underway. Second-line chemotherapy is likewise being challenged in phase III trials, one of which having recently reported positive results in advanced squamous cell carcinoma. In tumors harboring actionable transforming genetic alterations such as EGFR mutations and ALK rearrangements, second- and third-generation inhibitors allow for multiple lines of targeted treatment beyond initial resistance, postponing the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as a longstanding but still present standard of care capable of prolonging survival, improving quality of life, and relieving symptoms sees its role increasingly restricted to clinical, immunological, and molecular subsets of patients where its activity and efficacy have never been tested prospectively.

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Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC.

Cited by 53 publications

References 0 publications

Immunologic Checkpoint Blockade in Lung Cancer

Immunologic Checkpoint Blockade in Lung Cancer

Induced Pluripotent Stem Cell–conditioned Medium Suppressed Melanoma Tumorigenicity Through the Enhancement of Natural-Killer Cellular Immunity

Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer

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