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1. Detection and localization of early- and late-stage cancers using platelet RNA

Author

Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Afd Pharmaceutics, In ’t Veld, Sjors G.J.G., Arkani, Mohammad, Post, Edward, Antunes-Ferreira, Mafalda, D'Ambrosi, Silvia, Vessies, Daan C.L., Vermunt, Lisa, Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Tannous, Jihane, Meijer, Laura L., Le Large, Tessa Y.S., Mantini, Giulia, Wondergem, Niels E., Heinhuis, Kimberley M., van Wilpe, Sandra, Smits, A. Josien, Drees, Esther E.E., Roos, Eva, Leurs, Cyra E., Tjon Kon Fat, Lee Ann, van der Lelij, Ewoud J., Dwarshuis, Govert, Kamphuis, Maarten J., Visser, Lisanne E., Harting, Romee, Gregory, Annemijn, Schweiger, Markus W., Wedekind, Laurine E., Ramaker, Jip, Zwaan, Kenn, Verschueren, Heleen, Bahce, Idris, de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M., Hartemink, Koen J., Kuijpers, Marijke J.E., oude Egbrink, Mirjam G.A., Griffioen, Arjan W., Rossel, Rafael, Hiltermann, T. Jeroen N., Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., De Witt Hamer, Philip C., Kouwenhoven, Mathilde, Reijneveld, Jaap C., Leenders, William P.J., Hoeben, Ann, Verdonck-de Leeuw, Irma M., Leemans, C. René, Baatenburg de Jong, Robert J., Terhaard, Chris H.J., Takes, Robert P., Langendijk, Johannes A., de Jager, Saskia C., Kraaijeveld, Adriaan O., Pasterkamp, Gerard, Smits, Minke, Schalken, Jack A., Łapińska-Szumczyk, Sylwia, Łojkowska, Anna, Żaczek, Anna J., Lokhorst, Henk, van de Donk, Niels W.C.J., Nijhof, Inger, Prins, Henk Jan, Zijlstra, Josée M., Idema, Sander, Baayen, Johannes C., Teunissen, Charlotte E., Killestein, Joep, Besselink, Marc G., Brammen, Lindsay, Bachleitner-Hofmann, Thomas, Mateen, Farrah, Plukker, John T.M., Heger, Michal, de Mast, Quirijn, Lisman, Ton, Pegtel, D. Michiel, Bogaard, Harm Jan, Jassem, Jacek, Supernat, Anna, Mehra, Niven, Gerritsen, Winald, de Kroon, Cornelis D., Lok, Christianne A.R., Piek, Jurgen M.J., Steeghs, Neeltje, van Houdt, Winan J., Brakenhoff, Ruud H., Sonke, Gabe S., Verheul, Henk M., Giovannetti, Elisa, Kazemier, Geert, Sabrkhany, Siamack, Schuuring, Ed, Sistermans, Erik A., Wolthuis, Rob, Meijers-Heijboer, Hanne, Dorsman, Josephine, Oudejans, Cees, Ylstra, Bauke, Westerman, Bart A., van den Broek, Daan, Koppers-Lalic, Danijela, Wesseling, Pieter, Nilsson, R. Jonas A., Vandertop, W. Peter, Noske, David P., Tannous, Bakhos A., Sol, Nik, Best, Myron G., Wurdinger, Thomas, Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Afd Pharmaceutics, In ’t Veld, Sjors G.J.G., Arkani, Mohammad, Post, Edward, Antunes-Ferreira, Mafalda, D'Ambrosi, Silvia, Vessies, Daan C.L., Vermunt, Lisa, Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Tannous, Jihane, Meijer, Laura L., Le Large, Tessa Y.S., Mantini, Giulia, Wondergem, Niels E., Heinhuis, Kimberley M., van Wilpe, Sandra, Smits, A. Josien, Drees, Esther E.E., Roos, Eva, Leurs, Cyra E., Tjon Kon Fat, Lee Ann, van der Lelij, Ewoud J., Dwarshuis, Govert, Kamphuis, Maarten J., Visser, Lisanne E., Harting, Romee, Gregory, Annemijn, Schweiger, Markus W., Wedekind, Laurine E., Ramaker, Jip, Zwaan, Kenn, Verschueren, Heleen, Bahce, Idris, de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M., Hartemink, Koen J., Kuijpers, Marijke J.E., oude Egbrink, Mirjam G.A., Griffioen, Arjan W., Rossel, Rafael, Hiltermann, T. Jeroen N., Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., De Witt Hamer, Philip C., Kouwenhoven, Mathilde, Reijneveld, Jaap C., Leenders, William P.J., Hoeben, Ann, Verdonck-de Leeuw, Irma M., Leemans, C. René, Baatenburg de Jong, Robert J., Terhaard, Chris H.J., Takes, Robert P., Langendijk, Johannes A., de Jager, Saskia C., Kraaijeveld, Adriaan O., Pasterkamp, Gerard, Smits, Minke, Schalken, Jack A., Łapińska-Szumczyk, Sylwia, Łojkowska, Anna, Żaczek, Anna J., Lokhorst, Henk, van de Donk, Niels W.C.J., Nijhof, Inger, Prins, Henk Jan, Zijlstra, Josée M., Idema, Sander, Baayen, Johannes C., Teunissen, Charlotte E., Killestein, Joep, Besselink, Marc G., Brammen, Lindsay, Bachleitner-Hofmann, Thomas, Mateen, Farrah, Plukker, John T.M., Heger, Michal, de Mast, Quirijn, Lisman, Ton, Pegtel, D. Michiel, Bogaard, Harm Jan, Jassem, Jacek, Supernat, Anna, Mehra, Niven, Gerritsen, Winald, de Kroon, Cornelis D., Lok, Christianne A.R., Piek, Jurgen M.J., Steeghs, Neeltje, van Houdt, Winan J., Brakenhoff, Ruud H., Sonke, Gabe S., Verheul, Henk M., Giovannetti, Elisa, Kazemier, Geert, Sabrkhany, Siamack, Schuuring, Ed, Sistermans, Erik A., Wolthuis, Rob, Meijers-Heijboer, Hanne, Dorsman, Josephine, Oudejans, Cees, Ylstra, Bauke, Westerman, Bart A., van den Broek, Daan, Koppers-Lalic, Danijela, Wesseling, Pieter, Nilsson, R. Jonas A., Vandertop, W. Peter, Noske, David P., Tannous, Bakhos A., Sol, Nik, Best, Myron G., and Wurdinger, Thomas

Published
2022

2. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

Author

Best, Myron G., Sol, Nik, In ‘t Veld, Sjors G.J.G., Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Fejes, Aniko V., Tjon Kon Fat, Lee Ann, Huis in 't Veld, Anna E, Leurs, Cyra, Le Large, Tessa Y., Meijer, Laura L., Kooi, Irsan E., Rustenburg, François, Schellen, Pepijn, Verschueren, Heleen, Post, Edward, Wedekind, Laurine E., Bracht, Jillian, Esenkbrink, Michelle, Wils, Leon, Favaro, Francesca, Schoonhoven, Jilian D., Tannous, Jihane, Meijers-Heijboer, Hanne, Kazemier, Geert, Giovannetti, Elisa, Reijneveld, Jaap C., Idema, Sander, Killestein, Joep, Heger, Michal, de Jager, Saskia C., Urbanus, Rolf T., Hoefer, Imo E., Pasterkamp, Gerard, Mannhalter, Christine, Gomez-Arroyo, Jose, Bogaard, Harm-Jan, Noske, David P., Vandertop, W. Peter, van den Broek, Daan, Ylstra, Bauke, Nilsson, R. Jonas A, Wesseling, Pieter, Karachaliou, Niki, Rosell, Rafael, Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., Tannous, Bakhos A., de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M, Wurdinger, Thomas, Best, Myron G., Sol, Nik, In ‘t Veld, Sjors G.J.G., Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Fejes, Aniko V., Tjon Kon Fat, Lee Ann, Huis in 't Veld, Anna E, Leurs, Cyra, Le Large, Tessa Y., Meijer, Laura L., Kooi, Irsan E., Rustenburg, François, Schellen, Pepijn, Verschueren, Heleen, Post, Edward, Wedekind, Laurine E., Bracht, Jillian, Esenkbrink, Michelle, Wils, Leon, Favaro, Francesca, Schoonhoven, Jilian D., Tannous, Jihane, Meijers-Heijboer, Hanne, Kazemier, Geert, Giovannetti, Elisa, Reijneveld, Jaap C., Idema, Sander, Killestein, Joep, Heger, Michal, de Jager, Saskia C., Urbanus, Rolf T., Hoefer, Imo E., Pasterkamp, Gerard, Mannhalter, Christine, Gomez-Arroyo, Jose, Bogaard, Harm-Jan, Noske, David P., Vandertop, W. Peter, van den Broek, Daan, Ylstra, Bauke, Nilsson, R. Jonas A, Wesseling, Pieter, Karachaliou, Niki, Rosell, Rafael, Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., Tannous, Bakhos A., de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M, and Wurdinger, Thomas

Published
2017

3. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

Author

UMC Utrecht, Experimentele Afd. Cardiologie 2, CDL Staf Research, Circulatory Health, CDL Arcadia, CDL Cluster Onderzoek en Onderwijs, Pathologie Groep Moelans, Pathologie Pathologen staf, Arts Assistenten Longziekten, Arts-assistenten Radiologie, Brain, Best, Myron G., Sol, Nik, In ‘t Veld, Sjors G.J.G., Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Fejes, Aniko V., Tjon Kon Fat, Lee Ann, Huis in 't Veld, Anna E, Leurs, Cyra, Le Large, Tessa Y., Meijer, Laura L., Kooi, Irsan E., Rustenburg, François, Schellen, Pepijn, Verschueren, Heleen, Post, Edward, Wedekind, Laurine E., Bracht, Jillian, Esenkbrink, Michelle, Wils, Leon, Favaro, Francesca, Schoonhoven, Jilian D., Tannous, Jihane, Meijers-Heijboer, Hanne, Kazemier, Geert, Giovannetti, Elisa, Reijneveld, Jaap C., Idema, Sander, Killestein, Joep, Heger, Michal, de Jager, Saskia C., Urbanus, Rolf T., Hoefer, Imo E., Pasterkamp, Gerard, Mannhalter, Christine, Gomez-Arroyo, Jose, Bogaard, Harm-Jan, Noske, David P., Vandertop, W. Peter, van den Broek, Daan, Ylstra, Bauke, Nilsson, R. Jonas A, Wesseling, Pieter, Karachaliou, Niki, Rosell, Rafael, Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., Tannous, Bakhos A., de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M, Wurdinger, Thomas, UMC Utrecht, Experimentele Afd. Cardiologie 2, CDL Staf Research, Circulatory Health, CDL Arcadia, CDL Cluster Onderzoek en Onderwijs, Pathologie Groep Moelans, Pathologie Pathologen staf, Arts Assistenten Longziekten, Arts-assistenten Radiologie, Brain, Best, Myron G., Sol, Nik, In ‘t Veld, Sjors G.J.G., Vancura, Adrienne, Muller, Mirte, Niemeijer, Anna Larissa N., Fejes, Aniko V., Tjon Kon Fat, Lee Ann, Huis in 't Veld, Anna E, Leurs, Cyra, Le Large, Tessa Y., Meijer, Laura L., Kooi, Irsan E., Rustenburg, François, Schellen, Pepijn, Verschueren, Heleen, Post, Edward, Wedekind, Laurine E., Bracht, Jillian, Esenkbrink, Michelle, Wils, Leon, Favaro, Francesca, Schoonhoven, Jilian D., Tannous, Jihane, Meijers-Heijboer, Hanne, Kazemier, Geert, Giovannetti, Elisa, Reijneveld, Jaap C., Idema, Sander, Killestein, Joep, Heger, Michal, de Jager, Saskia C., Urbanus, Rolf T., Hoefer, Imo E., Pasterkamp, Gerard, Mannhalter, Christine, Gomez-Arroyo, Jose, Bogaard, Harm-Jan, Noske, David P., Vandertop, W. Peter, van den Broek, Daan, Ylstra, Bauke, Nilsson, R. Jonas A, Wesseling, Pieter, Karachaliou, Niki, Rosell, Rafael, Lee-Lewandrowski, Elizabeth, Lewandrowski, Kent B., Tannous, Bakhos A., de Langen, Adrianus J., Smit, Egbert F., van den Heuvel, Michel M, and Wurdinger, Thomas

Published
2017

4. Detection and localization of early- and late-stage cancers using platelet RNA.

Author

In 't Veld SGJG, Arkani M, Post E, Antunes-Ferreira M, D'Ambrosi S, Vessies DCL, Vermunt L, Vancura A, Muller M, Niemeijer AN, Tannous J, Meijer LL, Le Large TYS, Mantini G, Wondergem NE, Heinhuis KM, van Wilpe S, Smits AJ, Drees EEE, Roos E, Leurs CE, Tjon Kon Fat LA, van der Lelij EJ, Dwarshuis G, Kamphuis MJ, Visser LE, Harting R, Gregory A, Schweiger MW, Wedekind LE, Ramaker J, Zwaan K, Verschueren H, Bahce I, de Langen AJ, Smit EF, van den Heuvel MM, Hartemink KJ, Kuijpers MJE, Oude Egbrink MGA, Griffioen AW, Rossel R, Hiltermann TJN, Lee-Lewandrowski E, Lewandrowski KB, De Witt Hamer PC, Kouwenhoven M, Reijneveld JC, Leenders WPJ, Hoeben A, Verdonck-de Leeuw IM, Leemans CR, Baatenburg de Jong RJ, Terhaard CHJ, Takes RP, Langendijk JA, de Jager SC, Kraaijeveld AO, Pasterkamp G, Smits M, Schalken JA, Łapińska-Szumczyk S, Łojkowska A, Żaczek AJ, Lokhorst H, van de Donk NWCJ, Nijhof I, Prins HJ, Zijlstra JM, Idema S, Baayen JC, Teunissen CE, Killestein J, Besselink MG, Brammen L, Bachleitner-Hofmann T, Mateen F, Plukker JTM, Heger M, de Mast Q, Lisman T, Pegtel DM, Bogaard HJ, Jassem J, Supernat A, Mehra N, Gerritsen W, de Kroon CD, Lok CAR, Piek JMJ, Steeghs N, van Houdt WJ, Brakenhoff RH, Sonke GS, Verheul HM, Giovannetti E, Kazemier G, Sabrkhany S, Schuuring E, Sistermans EA, Wolthuis R, Meijers-Heijboer H, Dorsman J, Oudejans C, Ylstra B, Westerman BA, van den Broek D, Koppers-Lalic D, Wesseling P, Nilsson RJA, Vandertop WP, Noske DP, Tannous BA, Sol N, Best MG, and Wurdinger T

Subjects
Biomarkers, Tumor genetics, Blood Platelets, Early Detection of Cancer methods, Humans, Neoplasms diagnosis, Neoplasms genetics, RNA genetics
Abstract

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening., Competing Interests: Declaration of interests M.G. Best, R.J.A.N., and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc., and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2022
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5. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets.

Author

Best MG, Sol N, In 't Veld SGJG, Vancura A, Muller M, Niemeijer AN, Fejes AV, Tjon Kon Fat LA, Huis In 't Veld AE, Leurs C, Le Large TY, Meijer LL, Kooi IE, Rustenburg F, Schellen P, Verschueren H, Post E, Wedekind LE, Bracht J, Esenkbrink M, Wils L, Favaro F, Schoonhoven JD, Tannous J, Meijers-Heijboer H, Kazemier G, Giovannetti E, Reijneveld JC, Idema S, Killestein J, Heger M, de Jager SC, Urbanus RT, Hoefer IE, Pasterkamp G, Mannhalter C, Gomez-Arroyo J, Bogaard HJ, Noske DP, Vandertop WP, van den Broek D, Ylstra B, Nilsson RJA, Wesseling P, Karachaliou N, Rosell R, Lee-Lewandrowski E, Lewandrowski KB, Tannous BA, de Langen AJ, Smit EF, van den Heuvel MM, and Wurdinger T

Subjects
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Non-Small-Cell Lung genetics, Cohort Studies, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Inflammation blood, Inflammation diagnosis, Inflammation genetics, Lung Neoplasms blood, Lung Neoplasms genetics, Male, Middle Aged, Support Vector Machine, Algorithms, Artificial Intelligence, Blood Platelets physiology, Carcinoma, Non-Small-Cell Lung diagnosis, Diagnosis, Computer-Assisted methods, Lung Neoplasms diagnosis
Abstract

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2017
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6. Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor.

Author

van den Berg JH, Gomez-Eerland R, van de Wiel B, Hulshoff L, van den Broek D, Bins A, Tan HL, Harper JV, Hassan NJ, Jakobsen BK, Jorritsma A, Blank CU, Schumacher TN, and Haanen JB

Subjects
Adult, Cell- and Tissue-Based Therapy methods, Fatal Outcome, Female, Humans, Immunotherapy, Adoptive methods, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, MART-1 Antigen metabolism, Melanoma diagnosis, Melanoma genetics, Melanoma immunology, Melanoma therapy, Neoplasm Staging, Receptors, Antigen, T-Cell metabolism, Transduction, Genetic, Cell- and Tissue-Based Therapy adverse effects, Immunotherapy, Adoptive adverse effects, MART-1 Antigen immunology, Receptors, Antigen, T-Cell genetics, T-Cell Antigen Receptor Specificity immunology, T-Lymphocytes immunology, T-Lymphocytes metabolism
Abstract

Here, we describe a fatal serious adverse event observed in a patient infused with autologous T-cell receptor (TCR) transduced T cells. This TCR, originally obtained from a melanoma patient, recognizes the well-described HLA-A*0201 restricted 26-35 epitope of MART-1, and was not affinity enhanced. Patient 1 with metastatic melanoma experienced a cerebral hemorrhage, epileptic seizures, and a witnessed cardiac arrest 6 days after cell infusion. Three days later, the patient died from multiple organ failure and irreversible neurologic damage. After T-cell infusion, levels of IL-6, IFN-γ, C-reactive protein (CRP), and procalcitonin increased to extreme levels, indicative of a cytokine release syndrome or T-cell-mediated inflammatory response. Infused T cells could be recovered from blood, broncho-alveolar lavage, ascites, and after autopsy from tumor sites and heart tissue. High levels of NT-proBNP indicate semi-acute heart failure. No cross reactivity of the modified T cells toward a beating cardiomyocyte culture was observed. Together, these observations suggest that high levels of inflammatory cytokines alone or in combination with semi-acute heart failure and epileptic seizure may have contributed substantially to the occurrence of the acute and lethal event. Protocol modifications to limit the risk of T-cell activation-induced toxicity are discussed.

Published
2015
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