13 results on '"Sanmamed, Miguel F."'
Search Results
2. Contributors
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Batruch, Ihor, primary, Blonder, Josip, additional, Boccard, Julien, additional, Boschetti, Egisto, additional, Brenner, Dean E., additional, Caprioli, Richard M., additional, Castillo, Mary Joan, additional, Chan, Eric Chun Yong, additional, Cho, Wonryeon, additional, Cline, Erika N., additional, Codesido, Santiago, additional, Diamandis, Eleftherios P., additional, Djukovic, Danijel, additional, Drabovich, Andrei P., additional, Fox, Stephen D., additional, Gika, Helen G., additional, González-Ruiz, Víctor, additional, Goo, Young Ah, additional, Goodlett, David R., additional, Gowda, Nagana, additional, Issaq, Haleem J., additional, Kaczmarczyk, Jan A., additional, Kim, JinHee, additional, Lee, Cheng S., additional, Lilley, Laura M., additional, Llorente, Alicia, additional, Long, Frederick H., additional, Luke, Brian, additional, McShane, Adam J., additional, Melero, Ignacio, additional, Mukundan, Harshini, additional, Narasimhan, Meena L., additional, Nissley, Dwight V., additional, Patiño-García, Ana, additional, Patrie, Steven M., additional, Pavlou, Maria P., additional, Perez-Gracia, Jose Luis, additional, Plumb, Robert, additional, Prieto, DaRue A., additional, Raftery, Daniel, additional, Regnier, Fred E., additional, Righetti, Pier Giorgio, additional, Rudaz, Serge, additional, Sanmamed, Miguel F., additional, Saul, Richard G., additional, Seeley, Erin H., additional, Stromberg, Loreen R., additional, Theodoridis, Georgios A., additional, Tuck, Melissa, additional, Turgeon, D. Kim, additional, Van, Que N., additional, Veenstra, Timothy D., additional, Vuckovic, Dajana, additional, Wang, Chenchen, additional, Wang, Lei, additional, Whiteley, Gordon R., additional, Wilson, Ian D., additional, Yao, Xudong, additional, Ye, Xiaoying, additional, and Yip, Lian Yee, additional
- Published
- 2020
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3. Designing clinical studies for biomarker discovery: The Design criteria
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Perez-Gracia, Jose Luis, primary, Sanmamed, Miguel F., additional, Patiño-García, Ana, additional, and Melero, Ignacio, additional
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- 2020
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4. CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Bristol-Myers Squibb, European Commission, Asociación Española Contra el Cáncer, Fundación la Caixa, Teijeira, Alvaro, Garasa, Saray, Gato, María, Alfaro, Carlos, Migueliz, Itziar, Cirella, Assunta, Andrea, Carlos de, Ochoa, Maria Carmen, Otano, Itziar, Etxeberria, Iñaki, Andueza, María Pilar, Nieto, Celia P., Resano, Leyre, Azpilikueta, Arantza, Allegretti, Marcello, Pizzol, María de, Ponz-Sarvisé, Mariano, Rouzaut, Ana, Sanmamed, Miguel F., Schalper, Kurt, Carleton, Michael, Mellado, Mario, Rodriguez-Ruiz, María E., Berraondo, Pedro, Perez-Gracia, Jose L., Melero, Ignacio, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Bristol-Myers Squibb, European Commission, Asociación Española Contra el Cáncer, Fundación la Caixa, Teijeira, Alvaro, Garasa, Saray, Gato, María, Alfaro, Carlos, Migueliz, Itziar, Cirella, Assunta, Andrea, Carlos de, Ochoa, Maria Carmen, Otano, Itziar, Etxeberria, Iñaki, Andueza, María Pilar, Nieto, Celia P., Resano, Leyre, Azpilikueta, Arantza, Allegretti, Marcello, Pizzol, María de, Ponz-Sarvisé, Mariano, Rouzaut, Ana, Sanmamed, Miguel F., Schalper, Kurt, Carleton, Michael, Mellado, Mario, Rodriguez-Ruiz, María E., Berraondo, Pedro, Perez-Gracia, Jose L., and Melero, Ignacio
- Abstract
Extrusion of neutrophil extracellular traps (NETs) constitutes an adhesive mechanism employed by polymorphonuclear leukocytes in microbial defense and plays a role in cancer metastasis. Teijeira et al. show that intratumoral NETs protect malignant cells against cytotoxic attacks of the immune system, such as those elicited by checkpoint-based immunotherapy.Neutrophils are expanded and abundant in cancer-bearing hosts. Under the influence of CXCR1 and CXCR2 chemokine receptor agonists and other chemotactic factors produced by tumors, neutrophils, and granulocytic myeloid-derived suppressor cells (MDSCs) from cancer patients extrude their neutrophil extracellular traps (NETs). In our hands, CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted NETosis. NETs wrap and coat tumor cells and shield them from cytotoxicity, as mediated by CD8 T cells and natural killer (NK) cells, by obstructing contact between immune cells and the surrounding target cells. Tumor cells protected from cytotoxicity by NETs underlie successful cancer metastases in mice and the immunotherapeutic synergy of protein arginine deiminase 4 (PAD4) inhibitors, which curtail NETosis with immune checkpoint inhibitors. Intravital microscopy provides evidence of neutrophil NETs interfering cytolytic cytotoxic T lymphocytes (CTLs) and NK cell contacts with tumor cells.
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- 2020
5. PSA reactivity in extracellular microvesicles to commercial immunoassays.
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Sandúa A, Sanmamed MF, Rodríguez M, Ancizu-Marckert J, Gúrpide A, Perez-Gracia JL, Alegre E, and González Á
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- Male, Humans, Prostate-Specific Antigen, Immunoassay, Prostatic Hyperplasia diagnosis, Prostatic Neoplasms diagnosis, Cell-Derived Microparticles
- Abstract
Aims: Characterization of PSA in extracellular microvesicles (EVs) and its reactivity to commercial methods., Materials and Methods: EVs derived from serum of 47 prostate cancer (PCa) patients, 27 benign prostatic hyperplasia (BPH) patients and 42 healthy controls were analyzed. EVs isolation and quantification of PSA immunoreactive to total (ev-T-PSA) or free (ev-F-PSA) PSA immunoassays, were performed using commercial assays. PSA in CD81+ or CD63+ EVs was determined directly in serum by an immunocapture-ELISA (IC-ELISA)., Results: Ev-T-PSA immunoreactive to Elecsys assay was detected in all samples. Median T-PSA ev/srm ratio was 2.20 % (Q1-Q3: 0.80-4.00 %), although in some samples this ratio reached 59 %. T-PSA ev/srm ratio was higher in those samples with serum T-PSA below 4 µg/L than in those exceeding that cut-off (p < 0.001). T-PSA ev/srm ratio was lower in PCa patients compared to healthy controls and BPH patients (p < 0.001). Elecsys immunoassays detected higher concentrations of ev-T-PSA and ev-F-PSA than Immulite (p < 0.001). PSA was detected by IC-ELISA more intensely in CD81+ EVs than in CD63+ EVs, and ev-T-PSA correlated with PSA+ CD63+ (p < 0.001) but not with PSA+ CD81+., Conclusion: EVs-bound PSA is another form of circulating PSA whose measurement could be easily performed in clinical laboratories by automated immunoassays., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Miguel F Sanmamed received grants from Roche and BMS, not related to this work. María Rodríguez received speaker’s bureau honoraria from BMS and ROCHE, support for attending meeting from Roche, Astrazeneca, Catalym, and BMS, and research materials from Roche and Highlight Therapeutics, not related to this work. José L Pérez-Gracia has received grants from Roche, BMS, MSD and Seattle Genetics, not related to this work, and is a member of speaker bureau and advisory boards from Roche, BMS, Ipsen, MSD and Seattle Genetics. He has received travel support from Roche, MSD and BMS. Álvaro González has received support from Roche Diagnostics for attending Euromedlab 2021., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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6. ESMO Clinical Research Observatory (ECRO): improving the efficiency of clinical research through rationalisation of bureaucracy.
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Perez-Gracia JL, Awada A, Calvo E, Amaral T, Arkenau HT, Gruenwald V, Bodoky G, Lolkema MP, Di Nicola M, Penel N, Vera R, Sanmamed MF, and Douillard JY
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- Humans, Guidelines as Topic, Research Design, Research Personnel
- Abstract
During the last years, there has been a dramatic increase in the administrative and bureaucratic burden associated with clinical research, which has clearly had an impact on its overall efficiency and on the activity of clinical investigators and research teams. Indeed, the supervision of the adherence of clinical research to Good Clinical Practice (GCP) guidelines and legal regulations is of the utmost importance. Yet, while such regulations have remained largely unchanged during recent years, the number of administrative tasks and their complexity have grown markedly, as supported by the results of a survey performed among 940 clinical investigators that we report in this manuscript. Therefore, many investigators believe that it has become necessary to undertake a rigorous analysis of the causes and consequences of this issue, and to create a conduit to channel the advice from experienced investigators regarding clinical research procedures, in order to improve them. Based on these premises, ESMO has launched the ESMO Clinical Research Observatory (ECRO), a task force that will analyse different aspects of clinical research. ECRO will aim to provide the views of ESMO on clinical research procedures based on the feedback from clinical investigators, under complete adherence to the Declaration of Helsinki, the GCP guidelines and any other applicable legal regulations, while at the same time showing profound respect for all the stakeholders involved in clinical research. This manuscript provides the background and rationale for the creation of ECRO, its planned activity and an analysis of the current administrative burden in clinical research with recommendations to rationalise it. Indeed, we expect that this effort shall lead to a relevant improvement in the care of patients and in the development of clinical research., Competing Interests: Competing interests: JLP-G: Research grants and support: Roche, BMS, MSD, Ipsen, Eisai, Incyte, Janssen. Speakers bureau and advisory boards: Roche, BMS, Ipsen, Eisai, MSD, Seattle Genetics. Travel support: Roche, MSD, BMS. AA: Advisory role, research grants to my Institute. Speaker fees: Roche, Lilly, Amgen, EISAI, BMS, Pfizer, Novartis, MSD, Genomic Health, Ipsen, AstraZeneca, Bayer, Leo Pharma. EC: Honoraria or consultation fees: Astellas, Novartis, Nanobiotix, Pfizer, Janssen-Cilag, GLG, PsiOxus Therapeutics, Merck, Medscape, BMS, Gilead, Seattle Genetics, Pierre Fabre, Boehringer Ingelheim, Cerulean Pharma, EUSA, Gehrmann Consulting, AstraZeneca, Roche, Guidepoint, Servier, Celgene, Abbvie, Amcure, OncoDNA, Alkermes. Leadership role: Director, Clinical Research, START Madrid, Director, Clinical Research, HM Hospitals Group, Madrid. Stocks or ownership: START, Oncoart Associated, International Cancer Consultants. Licensing fees or royalties: None. Direct research funding as project lead: Novartis, AstraZeneca, Beigene. Institutional financial support from clinical trials: Abbvie, ACEO, Amcure, AMGEN, AstraZeneca, BMS, Cytomx, GSK, Genentech/Roche, H3, Incyte, Janssen, Kura. Lilly, Loxo, Nektar, Macrogenics, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, PUMA, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Takeda, Incyte, Innovio, MSD, PsiOxus, Seattle Genetics, Mersana, GSK, Daiichi, Nektar, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharm, Boehringen Ingelheim, Regeneron, Millenium, Synthon, Spectrum, Rigontec. Non-financial interests: Scientific board at PsiOxus. Leadership in medical society: Founder and president, non-for-profit Foundation INTHEOS (Investigational Therapeutics in Oncological Sciences). Memberships: SEOM, EORTC, ESMO, ASCO. Other relationships: HM Hospitals Group and START, Program of Early Phase Clinical Drug Development in Oncology, Employee: Medical Oncologist, Director, Clinical Research. Methods in Clinical Cancer Research (MCCR) Workshop, Zeist, Netherlands (Joint ECCO-AACR-EORTC-ESMO Workshop on Methods in Clinical Cancer, Research), Co-director. TA: travel grants from Novartis, personal fees and travel grants from BMS, personal fees from Pierre Fabre and research grant from Neracare, outside the submitted work. H-TA: Research Support to Employer: Employee of HCA Healthcare UK and Sarah Cannon Research Institute. Advisory Boards: Roche, Servier, Merck Serono, Biontech, Bicycle, Taiho, Beigene, Iovance, Bayer, Guardant. VG: honoraria for lectures and advisory role: AstraZeneca, Bayer, BMS, EUSAPharm, Ipsen, Pfizer, MSD, Lilly, PharmaMar. Novartis, Nanobiotix, MerckSerono, Janssen-Cliag, Exelexis, Roche, Eisai, Cerulean. Research funding: AstraZeneca, BMS, Novartis, MSD, Pfizer. GB: Advisory board and speakers bureau: Pfizer, Novartis Roche Servier Janssen Ipsen Lilly Amgen Merck. Travel support: Pfizer Janssen Roche MSD. MPL: Research grants (to hospital) MSD/Astellas/JnJ/ Sanofi. Advice: Roche/ Bayer/Amgen/JnJ/ Sanofi/ Servier/Pfizer/ Incyte. MDN: Speakers bureau and advisory boards: BMS. Travel support: MSD, BMS. NP: Research grants and support: Bayer HealthCare, Roche, Sanofi. Speakers bureau and advisory boards: Astellas, Bayer HealtCare, Ipsen, Janssen Roche, Genetics. Travel support: Ipsen, Pharmamar. MFS: Research grants: Roche. RV: Speakers bureau and advisory boards: Roche, BMS, MERK, AMGEN, SANOFI, MSD, BAYER, SERVIER. Travel support: Roche, MSD, AMGEN, MERK, SANOFI, BAYER. J-YD: No conflict of interest to disclose., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)
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- 2020
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7. Are Immune Checkpoint Inhibitors Effective Against Uncommon Oncogene-Driven NSCLC Subtypes?
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Eguren-Santamaria I, Sanmamed MF, and Gil-Bazo I
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- Humans, Immunotherapy, Mutation, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins c-ret, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
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- 2020
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8. The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer.
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Lee JW, Zhang Y, Eoh KJ, Sharma R, Sanmamed MF, Wu J, Choi J, Park HS, Iwasaki A, Kaftan E, Chen L, Papadimitrakopoulou V, Herbst RS, and Koo JS
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- Adenocarcinoma of Lung immunology, Adenocarcinoma of Lung pathology, Animals, Antineoplastic Agents, Immunological administration & dosage, B7-H1 Antigen biosynthesis, B7-H1 Antigen immunology, Drug Synergism, Female, Lung Neoplasms immunology, Lung Neoplasms pathology, MAP Kinase Kinase Kinases antagonists & inhibitors, Mice, Mice, Knockout, Mice, Transgenic, Myeloid-Derived Suppressor Cells immunology, Myeloid-Derived Suppressor Cells pathology, Programmed Cell Death 1 Receptor biosynthesis, Programmed Cell Death 1 Receptor immunology, Protein Kinase Inhibitors administration & dosage, Pyridones pharmacology, Pyrimidinones pharmacology, Survival Analysis, Adenocarcinoma of Lung drug therapy, Adenocarcinoma of Lung genetics, Antineoplastic Agents, Immunological pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins p21(ras) genetics, Tumor Suppressor Protein p53 genetics
- Abstract
Introduction: This study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and to evaluate the combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or programmed cell death ligand 1 (PD-L1) in vivo., Methods: Trp53
FloxFlox ;KrasG12D/+ ;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were used to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase. Using these tumor-bearing lungs, tumor-infiltrating immune cells were characterized by both mass cytometry and flow cytometry. PKL-mediated immunocompetent syngeneic and transgenic lung cancer mouse models were treated with MEKi alone as well as in combination with either anti-PD-1 or anti-PD-L1 mAbs. Tumor growth and survival outcome were assessed. Finally, immune cell populations within spleens and tumors were evaluated by flow cytometry and immunohistochemistry., Results: Myeloid-derived suppressor cells (MDSCs) were significantly augmented in PKL-driven lung tumors compared to normal lungs of tumor-free mice. PD-L1 expression appeared to be highly positive in both lung tumor cells and, particularly MDSCs. The combinatory administration of MEKi with either anti-PD-1 or anti-PD-L1 mAbs synergistically increased antitumor response and survival outcome compared with single-agent therapy in both the PKL-mediated syngeneic and transgenic lung cancer models. Theses combinational treatments resulted in significant increases of tumor-infiltrating CD8+ and CD4+ T cells, whereas attenuation of CD11b+ /Gr-1high MDSCs, in particular, Ly6Ghigh polymorphonuclear-MDSCs in the syngeneic model., Conclusions: These findings suggest a potential therapeutic approach for untargetable Kras/p53-driven lung cancers with synergy between targeted therapy using MEKi and immunotherapies., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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9. Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies.
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Chester C, Sanmamed MF, Wang J, and Melero I
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- Animals, Humans, Antibodies, Monoclonal therapeutic use, Immunotherapy, Neoplasms drug therapy, Neoplasms immunology, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology
- Abstract
4-1BB (CD137, tumor necrosis factor receptor superfamily 9) is an inducible costimulatory receptor expressed on activated T and natural killer (NK) cells. 4-1BB ligation on T cells triggers a signaling cascade that results in upregulation of antiapoptotic molecules, cytokine secretion, and enhanced effector function. In dysfunctional T cells that have a decreased cytotoxic capacity, 4-1BB ligation demonstrates a potent ability to restore effector functions. On NK cells, 4-1BB signaling can increase antibody-dependent cell-mediated cytotoxicity. Agonistic monoclonal antibodies targeting 4-1BB have been developed to harness 4-1BB signaling for cancer immunotherapy. Preclinical results in a variety of induced and spontaneous tumor models suggest that targeting 4-1BB with agonist antibodies can lead to tumor clearance and durable antitumor immunity. Clinical trials of 2 agonist antibodies, urelumab and utomilumab, are ongoing. Despite initial signs of efficacy, clinical development of urelumab has been hampered by inflammatory liver toxicity at doses >1 mg/kg. Utomilumab has a superior safety profile, but is a less potent 4-1BB agonist relative to urelumab. Both antibodies have demonstrated promising results in patients with lymphoma and are being tested in combination therapy trials with other immunomodulatory agents. In an effort to optimally leverage 4-1BB-mediated immune activation, the next generation of 4-1BB targeting strategies attempts to decouple the observed antitumor efficacy from the on-target liver toxicity. Multiple therapeutics that attempt to restrict 4-1BB agonism to the tumor microenvironment and minimize systemic exposure have emerged. 4-1BB is a compelling target for cancer immunotherapy and future agents show great promise for achieving potent immune activation while avoiding limiting immune-related adverse events., (© 2018 by The American Society of Hematology.)
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- 2018
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10. Interleukin-8 in cancer pathogenesis, treatment and follow-up.
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Alfaro C, Sanmamed MF, Rodríguez-Ruiz ME, Teijeira Á, Oñate C, González Á, Ponz M, Schalper KA, Pérez-Gracia JL, and Melero I
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- Biomarkers, Tumor metabolism, Follow-Up Studies, Humans, Immunotherapy methods, Interleukin-8 metabolism, Neoplasms immunology, Neoplasms metabolism, Neoplasms therapy
- Abstract
Interleukin-8 (CXCL8) was originally described asa chemokine whose main function is the attraction of a polymorphonuclear inflammatory leukocyte infiltrate acting on CXCR1/2. Recently, it has been found that tumors very frequently coopt the production of this chemokine, which in this malignant context exerts different pro-tumoral functions. Reportedly, these include angiogenesis, survival signaling for cancer stem cells and attraction of myeloid cells endowed with the ability to immunosuppress and locally provide growth factors. Given the fact that in cancer patients IL-8 is mainly produced by tumor cells themselves, its serum concentration has been shown to correlate with tumor burden. Thus, IL-8 serum concentrations have been shown to be useful asa pharmacodynamic biomarker to early detect response to immunotherapy. Finally, because of the roles that IL-8 plays in favoring tumor progression, several therapeutic strategies are being developed to interfere with its functions. Such interventions hold promise, especially for therapeutic combinations in the field of cancer immunotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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11. Strategies to design clinical studies to identify predictive biomarkers in cancer research.
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Perez-Gracia JL, Sanmamed MF, Bosch A, Patiño-Garcia A, Schalper KA, Segura V, Bellmunt J, Tabernero J, Sweeney CJ, Choueiri TK, Martín M, Fusco JP, Rodriguez-Ruiz ME, Calvo A, Prior C, Paz-Ares L, Pio R, Gonzalez-Billalabeitia E, Gonzalez Hernandez A, Páez D, Piulats JM, Gurpide A, Andueza M, de Velasco G, Pazo R, Grande E, Nicolas P, Abad-Santos F, Garcia-Donas J, Castellano D, Pajares MJ, Suarez C, Colomer R, Montuenga LM, and Melero I
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- Anaplastic Lymphoma Kinase, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Biomedical Research standards, Clinical Studies as Topic, Clinical Trials as Topic, ErbB Receptors genetics, Humans, Mutation, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins c-kit genetics, Receptor Protein-Tyrosine Kinases genetics, Receptor, ErbB-2 analysis, ras Proteins genetics, Biomarkers, Tumor analysis, Biomedical Research methods
- Abstract
The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2017
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12. Orchestrating immune check-point blockade for cancer immunotherapy in combinations.
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Perez-Gracia JL, Labiano S, Rodriguez-Ruiz ME, Sanmamed MF, and Melero I
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- Animals, CTLA-4 Antigen immunology, Humans, Lymphocyte Activation, Neoplasms immunology, Programmed Cell Death 1 Receptor immunology, T-Lymphocytes immunology, Immunotherapy, Neoplasms therapy
- Abstract
Inhibitory receptors on immune system cells respond to membrane-bound and soluble ligands to abort or mitigate the intensity of immune responses by raising thresholds of activation, halting proliferation, favoring apoptosis or inhibiting/deviating effector function differentiation. Such evolutionarily selected inhibitory mechanisms are termed check-points and therefore check-point inhibitors empower any ongoing anti-cancer immune response that might have been too weak or exhausted. Monoclonal antibodies (mAb) interfering with CTLA-4-CD80/86, PD-1 - PD-L1, TIM-3-GAL9 and LAG3-MHC-II belong to this category of check-point inhibitors. The anti-CTLA-4 mAb ipilimumab has been approved for metastatic melanoma. Anti-PD-1 and anti-PD-L1 mAbs have shown extremely encouraging clinical activity. The potential of combination strategies with these agents has recently been highlighted by clinical observations on CTLA-4+PD-1 combined blockade in melanoma patients., (Copyright © 2014. Published by Elsevier Ltd.)
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- 2014
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13. Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy in metastatic melanoma patients.
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Sanmamed MF, Fernández-Landázuri S, Rodríguez C, Lozano MD, Echeveste JI, Pérez Gracia JL, Alegre E, Carranza O, Zubiri L, Martín-Algarra S, and González A
- Subjects
- Biomarkers, Tumor blood, Female, Humans, L-Lactate Dehydrogenase blood, Male, Melanoma blood, Melanoma diagnosis, Middle Aged, Neoplasm Metastasis, Prognosis, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Skin Neoplasms blood, Skin Neoplasms diagnosis, Treatment Outcome, Extracellular Matrix Proteins blood, Melanoma drug therapy, Melanoma pathology, Neoplasm Proteins blood, Proto-Oncogene Proteins B-raf antagonists & inhibitors, S100 Proteins blood, Skin Neoplasms drug therapy, Skin Neoplasms pathology
- Abstract
BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts clinical activity of BRAF inhibitors (iBRAF). We evaluated the role of MIA, S100 and LDH to monitor iBRAF efficiency in advanced melanoma patients presenting BRAF V600 mutations. This was a prospective study of melanoma patients harboring the BRAF V600 mutation and treated with iBRAF within a clinical trial (dabrafenib) or as part of an expanded access program (vemurafenib). MIA, S100 and LDH were analyzed in serum at baseline, and every 4-6 weeks during treatment. Eighteen patients with melanoma stages IIIc-IV were enrolled with 88.8% of response rate to iBRAF. Baseline concentrations of all the tumor markers correlated with tumor burden. MIA and S100 concentrations decreased significantly one month after the beginning of treatment and, upon progression, their concentrations increased significantly above the minimum levels previously achieved. MIA levels lower than 9 μg/L one month after the beginning of treatment and S100 concentrations lower than 0.1 μg/L at the moment of best response were associated with improved progression-free survival. In conclusion, MIA and S100 are useful to monitor response in melanoma patients treated with iBRAF., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
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