A personalized view on cancer immunotherapy

Wayteck, Laura; Breckpot, Karine; Demeester, Jo; Smedt, Stefaan C. De; Raemdonck, Koen

doi:10.1016/j.canlet.2013.09.016

Cited by 58 publications

(44 citation statements)

References 159 publications

(152 reference statements)

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“…Thus, improved TV sparing can likely decrease HT and increase the likelihood of full administration of chemotherapy, possibly resulting in improved outcomes. Additionally, given the future potential for immunotherapy to use a patient’s own immune system in the treatment of cancer, maximum preservation of BM function is necessary (42) and may be aided by better TV sparing.…”

Section: Discussionmentioning

confidence: 99%

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

Deek

Benenati

Kim

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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Purpose To determine the relationships between radiation doses to the thoracic bone marrow and declines in blood cell counts in non-small cell lung cancer (NSCLC) patients treated with chemoradiation therapy (CRT). Methods and Materials We included 52 patients with NSCLC treated with definitive concurrent carboplatinepaclitaxel and RT. Dose-volume histogram (DVH) parameters for the thoracic vertebrae (TV), sternum, scapulae, clavicles, and ribs were assessed for associations with changes in blood counts during the course of CRT. Linear and logistic regression analyses were performed to identify associations between hematologic nadirs and DVH parameters. A DVH parameter of Vx was the percentage of the total organ volume exceeding × radiation dose. Results Grade ≥3 hematologic toxicity including neutropenia developed in 21% (n=11), leukopenia in 42% (n=22), anemia in 6% (n=3), and throbocytopenia in 2% (n=1) of patients. Greater RT dose to the TV was associated with higher risk of grade ≥3 leukopenia across multiple DVH parameters, including TV V20 (TVV) (odds ratio [OR] 1.06; P=.025), TVV30 (OR 1.07; P=.013), and mean vertebral dose (MVD) (OR 1.13; P=.026). On multiple regression analysis, TVV30 (β = −0.004; P=.018) and TVV20 (β = 0.003; P=.048) were associated with white blood cell nadir. Additional bone marrow sites (scapulae, clavicles, and ribs) did not affect hematologic toxicity. A 20% chance of grade ≥3 leukopenia was associated with a MVD of 13.5 Gy and a TTV30 of 28%. Cutoff values to avoid grade ≤3 leukopenia were MVD ≤23.9 Gy, TVV20 ≤56.0%, and TVV30 ≤52.1%. Conclusions Hematologic toxicity is associated with greater RT doses to the TV during CRT for NSCLC. Sparing of the TV using advanced radiation techniques may improve tolerance of CRT and result in improved tolerance of concurrent chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

Deek

Benenati

Kim

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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“…Firstly, the immune system should be able to discriminate between healthy tissue and cancer cells. For this, it is crucial to load DCs with cancer-specific tumor associated antigens (TAAs) [3,4]. Upon presentation of these TAAs in major histocompatibility complexes (MHC) on the DC surface, TAA-specific immune responses can be mounted.…”

Section: Introductionmentioning

confidence: 99%

The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy

Dewitte

Lint

Heirman

et al. 2014

Journal of Controlled Release

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101

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Dendritic cell (DC)-based cancer vaccines, where the patient's own immune system is harnessed to target and destroy tumor tissue, has emerged as a potent therapeutic strategy. In the development of such DC vaccines, it is crucial to load the DCs with tumor antigens, and to simultaneously activate them to become more potent antigen-presenting cells. For this, we report on microbubbles, loaded with both antigen mRNA as well as immunomodulating TriMix mRNA, which can be used for the ultrasound-triggered transfection of DCs. In vivo experiments with in vitro sonoporated DCs, show the effective induction of antigen-specific T cells, resulting in specific lysis of antigen-expressing cells. Especially in a therapeutic setting, sonoporation with TriMix has a significant added value, resulting in a significant reduction of tumor outgrowth and a marked increase in overall survival. What is more, complete tumor regression was observed in 30% of the antigen+TriMix DC vaccinated animals, which also displayed long-term antigen-specific immunological memory. As a result, DC sonoporation using microbubbles loaded with a combination of antigen and TriMix mRNA can elicit powerful immune responses in vivo, and might serve as a potential tool for further in vivo DC vaccination applications.

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“…Of note, this review will focus on inducing antitumor immunity by targeting DCs. Excellent reviews on other promising strategies in immunotherapy, such as adoptive T cell therapy and immune checkpoint blockade, can be found in references [11][12][13].…”

Section: Introduction: Cancer Immunotherapy On the Risementioning

confidence: 99%

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

et al. 2014

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Over the years research in the field of cancer immunotherapy has flourished, bringing about crucial breakthroughs, but at the same time revealing new and important pathways of immune suppression that put a break on the success of cancer immunotherapy. This review focuses on how nano-and micromaterials can be used to induce antitumor immune responses and what their role in overcoming immune suppression could be. It is now beyond question that this requires elegantly designed particles that can reach their target cells, deliver antigenic cargo and most importantly immune stimulants in order to provoke and sustain antitumor immunity.3

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A personalized view on cancer immunotherapy

Cited by 58 publications

References 159 publications

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

Thoracic Vertebral Body Irradiation Contributes to Acute Hematologic Toxicity During Chemoradiation Therapy for Non-Small Cell Lung Cancer

The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

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