المؤلفون: Gastman, Brian, Agarwal, Piyush K, Berger, Adam, Boland, Genevieve, Broderick, Stephen, Butterfield, Lisa H, Byrd, David, Fecci, Peter E, Ferris, Robert L, Fong, Yuman, Goff, Stephanie L, Grabowski, Matthew M, Ito, Fumito, Lim, Michael, Lotze, Michael T, Mahdi, Haider, Malafa, Mokenge, Morris, Carol D, Murthy, Pranav, Neves, Rogerio I, Odunsi, Adekunle, Pai, Sara I, Prabhakaran, Sangeetha, Rosenberg, Steven A, Saoud, Ragheed, Sethuraman, Jyothi, Skitzki, Joseph, Slingluff, Craig L, Sondak, Vernon K, Sunwoo, John B, Turcotte, Simon, Yeung, Cecilia CS, Kaufman, Howard L

المصدر: Journal for ImmunoTherapy of Cancer. 8(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunization, Rare Diseases, Cancer, Clinical Research, Clinical Trials and Supportive Activities, Orphan Drug, Detection, screening and diagnosis, 4.5 Resources and infrastructure (detection), Good Health and Well Being, Clinical Trials as Topic, Humans, Immunotherapy, Medical Oncology, Tissue and Organ Procurement, biomarkers, tumor, guidelines as topic, review, clinical trials as topic, immunotherapy, Oncology and carcinogenesis

الوصف: Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells. There have been few guidelines or consensus statements on how to optimally collect and manage biospecimens and source material being used for immunotherapy and related research. The Society for Immunotherapy of Cancer Surgery Committee has brought together surgical experts from multiple subspecialty disciplines to identify best practices and to provide consensus on how best to access and manage specific tissues for immuno-oncology treatments and clinical investigation. In addition, the committee recommends early integration of surgeons and other interventional physicians with expertise in biospecimen collection, especially in clinical trials, to optimize the quality of tissue and the validity of correlative clinical studies in cancer immunotherapy.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5rj2916vTest

المؤلفون: Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N, Chow, Christine, Nazeran, Tayyebeh M, Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D, Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y, McCauley, Bryan M, Karpinskyj, Chloe, de Sousa, Christiani B, Høgdall, Claus, Tiezzi, Daniel G, Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M, Lester, Jenny, Rothstein, Joseph H, de Andrade, Jurandyr M, Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R, Garcia, Maria J, Intermaggio, Maria P, Alcaraz, Marie-Lyne, Brett, Mary A, Beckmann, Matthias W, Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E, Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B, Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y, Kaufmann, Scott H, Fereday, Sian, Gayther, Simon, Winham, Stacey J, Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A, McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B, Whittemore, Alice S, Staebler, Annette, Karlan, Beth Y, Rodriguez-Antona, Cristina, Bowtell, David D, Goode, Ellen L, Høgdall, Estrid, Candido Dos Reis, Francisco J, Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B, Kelemen, Linda E, Cook, Linda S, Goodman, Marc T, Fasching, Peter A, Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G, Köbel, Martin, Ramus, Susan J, Pharoah, Paul DP, Brenton, James D

المصدر: British journal of cancer. 123(5)

مصطلحات موضوعية: Oncology & Carcinogenesis, Oncology and Carcinogenesis, Public Health and Health Services

الوصف: BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1rg464jsTest

المؤلفون: Annapragada, Ananth, Sikora, Andrew, Bollard, Catherine, Conejo-Garcia, Jose, Cruz, Conrad Russell, Demehri, Shadmehr, Demetriou, Michael, Demirdjian, Levon, Fong, Lawrence, Horowitz, Mary, Hutson, Alan, Kadash-Edmondson, Kathryn, Kufe, Donald, Lipkin, Steven, Liu, Song, McCarthy, Claire, Morgan, Martin, Morris, Zachary, Pan, Yang, Pasquini, Marcelo, Schoenberger, Stephen, Van Allen, Eliezer, Vilar, Eduardo, Xing, Yi, Zha, Wenjuan, Consortium, the IOTN, Odunsi, Adekunle

المصدر: Journal for ImmunoTherapy of Cancer. 8(1)

مصطلحات موضوعية: Rare Diseases, Cancer, Biotechnology, Immunization, Prevention, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Humans, Immunotherapy, Medical Oncology, Neoplasms, immunotherapy, immunity, IOTN Consortium

الوصف: Despite regulatory approval of several immune-based treatments for cancer in the past decade, a number of barriers remain to be addressed in order to fully harness the therapeutic potential of the immune system and provide benefits for patients with cancer. As part of the Cancer Moonshot initiative, the Immuno-Oncology Translational Network (IOTN) was established to accelerate the translation of basic discoveries to improve immunotherapy outcomes across the spectrum of adult cancers and to develop immune-based approaches that prevent cancers before they occur. The IOTN currently consists of 32 academic institutions in the USA. By leveraging cutting-edge preclinical research in immunotherapy and immunoprevention, open data and resource sharing, and fostering highly collaborative team science across the immuno-oncology ecosystem, the IOTN is designed to accelerate the generation of novel mechanism-driven immune-based cancer prevention and therapies, and the development of safe and effective personalized immuno-oncology approaches.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8m90f217Test

المؤلفون: Odunsi, Adekunle Omatayo

مصطلحات موضوعية: 572.8, HPV vaccine design

الوصف: The human papilloma virus (HPY) infection has a causal association with cervical intraepithelial neoplasia (CIN) and cervical cancer. However, pre-malignant or malignant transformation is not always observed with HPY infection. lILA molecules are important in the regulation of the immune response to foreign antigens. The role of genetic variation at the HLA class II loci (DR and DQ) in CIN was investigated in 176 British Caucasian patients and 420 controls (normal cervical cytology and negative for HPY 16, 18, 31 and 33). HLA DQB 1 *03 typing was performed by a novel polymerase chain reactionrestriction fragment length polymorphism method (A-RFLP). The technique uses PCR to mutate the first base of codon 40 (DQ alleles) from T to G to create an artificial restriction site for an enzyme, MluI, which distinguishes DQB 1 *03 from other alleles and is confirmed by digestion of amplified DNA with Mlul. Further HLA DR-DQ typing was performed by PCR DNA amplification and oligonucleotide probe typing. HPY types (16, 18, 31 & 33) were detected by using type-specific oligonucleotide primers and PCR. The alleles of the DQB 1 *03, DRB 1 *04 and DRB 1 * 11 groups were strongly associated with susceptibility to CIN. Specifically the haplotypes DRB 1 *040 I-DQB 1 *0301 and DRBl*1101-DQB1*0301 were significant and indicated susceptibility. The DQBl*03 locus was more contributory to this association than the DRB 1 loci. A weak protective effect was shown for the haplotype DRB 1 *0 10 I-DQB 1 *0501. Positive correlation was also observed for HPY-positive CIN, suggesting that specific HLA alleles may be important in determining the immune response to HPY antigens and the risk for CIN after HPY infection. Immunoaffinity purification of the susceptibility and protective HLA ~ molecules was performed and the naturally processed peptides were eluted and sequenced by Edman degradation. The data obtained was used for motif prediction of HPY 16 E6, E7, Ll and L2 sequences that may be capable of binding to these HLA molecules. Motif prediction as well as the binding affinity of predicted peptide motifs for HLA D RB 1 *0401 and DRB 1 *0 10 1 was accomplished using the published data' on the naturally bound peptide sequences bound to these HLA molecules. The results revealed significant differences in both the number and binding affinity of the HPV 16 derived peptides to the protective and susceptibility HLA molecules. These results should help in the rational design of vaccines against HPV.

الإتاحة: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266420Test

المؤلفون: Martins, Filipe Correia, Couturier, Dominique-laurent, Paterson, Anna, Karnezis, Anthony N., Chow, Christine, Nazeran, Tayyebeh M., Odunsi, Adekunle, Gentry-maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D., Brooks-wilson, Angela, Defazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y., Mccauley, Bryan M., Karpinskyj, Chloe, De Sousa, Christiani B., Høgdall, Claus, Tiezzi, Daniel G., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M., Lester, Jenny, Rothstein, Joseph H., De Andrade, Jurandyr M., Lundvall, Lene, Paz-ares, Luis, Robles-díaz, Luis, Wilkens, Lynne R., Garcia, Maria J., Intermaggio, Maria P., Alcaraz, Marie-lyne, Brett, Mary A., Beckmann, Matthias W., Jimenez-linan, Mercedes, Anglesio, Michael, Carney, Michael E., Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B., Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y., Kaufmann, Scott H., Fereday, Sian, Gayther, Simon, Winham, Stacey J., Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A., Mcguire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B., Whittemore, Alice S., Staebler, Annette, Karlan, Beth Y., Rodriguez-antona, Cristina, Bowtell, David D., Goode, Ellen L., Høgdall, Estrid, Candido Dos Reis, Francisco J., Gronwald, Jacek, Chang-claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., Fasching, Peter A., Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G., Köbel, Martin, Ramus, Susan J., Pharoah, Paul D. P., Brenton, James D.

المصدر: Martins , F C , Couturier , D , Paterson , A , Karnezis , A N , Chow , C , Nazeran , T M , Odunsi , A , Gentry-maharaj , A , Vrvilo , A , Hein , A , Talhouk , A , Osorio , A , Hartkopf , A D , Brooks-wilson , A , Defazio , A , Fischer , A , Hartmann , A , Hernandez , B Y , Mccauley , B M , Karpinskyj , C , De Sousa , C B , Høgdall , C , Tiezzi , D ....

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1038/s41416-020-0900-0Test
https://curis.ku.dk/portal/da/publications/clinical-and-pathological-associations-of-pten-expression-in-ovarian-cancerTest(9a64dc4c-63d6-437f-90be-5e37cae902b6).html
https://curis.ku.dk/ws/files/260750252/s41416_020_0900_0.pdfTest

المؤلفون: Odunsi, Adekunle, McGray, A J Robert, Miliotto, Anthony, Zhang, Yali, Wang, Jianming, Abiola, Adebukola, Eppolito, Cheryl, Huang, Ruea-Yea

المساهمون: Roswell Park Alliance Foundation, Roswell Park Cancer Institute, Center for Strategic Scientific Initiatives, National Cancer Institute

المصدر: Journal for ImmunoTherapy of Cancer ; volume 8, issue 2, page e001237 ; ISSN 2051-1426

الوصف: Background Immune checkpoint blockers (ICBs) have been approved by the Food and Drug Administration to be used alone in front-line therapies or in combination with other regimens for certain advanced cancers. Since ICB only works in a subset of patients and has limited efficacy in treating ovarian cancer (OVC), developing preclinical models that help to understand which patients may derive benefit from ICB would be of tremendous benefit in OVC. Methods Here, we generated preclinical human OVC models from freshly resected tumors, which include six patient-derived xenografts (PDXs) from six different patient tumors, three transplantable OVC PD spheroid lines (PD-sphs), and 3 cell lines (PD-CLs). We tested the therapeutic combination of anti-PD1/CTLA4 antibodies with (1) autologous tumor-associated leukocytes (TALs) on the growth of PD-sphs in a coculture system in vitro, (2) with adoptively transferred autologous peripheral blood mononuclear cells or TALs in patient-derived OVC models using partially humanized mice, NSG-HHDxSGM3 (N-HSGM3). Results We show that PD-1 and CTLA-4 dual blockade when combined with autologous TALs effectively reduced PD-sph number in a co-culture system and led to regression of established PD-CLs and PDXs in the N-HSGM3 mice. Combinatorial PD-1 and CTLA-4 blockade increased the frequency and function of tumor-specific CD8 T cells. These CD8 T cells persisted in the tumor microenvironment, exhibited memory phenotype and protected animals from tumor growth on tumor rechallenge. Gene expression analysis of tumors resistant to dual PD1/CTLA4 blockade treatment identified upregulation of antigen processing and presentation pathways and downregulation of extracellular matrix organization genes. Conclusions These findings describe a novel platform for developing patient-derived preclinical tumor models suitable for rationally testing combinatorial ICB in the context of autologous tumor-reactive T cells. This platform can be further developed for testing additional targeted therapies relevant to ...

الإتاحة: https://doi.org/10.1136/jitc-2020-001237Test

المؤلفون: Qin, Maochun, Liu, Biao, Conroy, Jeffrey M, Morrison, Carl D, Hu, Qiang, Cheng, Yubo, Murakami, Mitsuko, Odunsi, Adekunle O, Johnson, Candace S, Wei, Lei, Liu, Song, Wang, Jianmin

المصدر: BMC Bioinformatics ; volume 16, issue 1 ; ISSN 1471-2105

مصطلحات موضوعية: Applied Mathematics, Computer Science Applications, Molecular Biology, Biochemistry, Structural Biology

الإتاحة: https://doi.org/10.1186/s12859-015-0502-7Test

المؤلفون: Martins, Filipe Correia, Couturier, Dominique-Laurent, Paterson, Anna, Karnezis, Anthony N., Chow, Christine, Nazeran, Tayyebeh M., Odunsi, Adekunle, Gentry-Maharaj, Aleksandra, Vrvilo, Aleksandra, Hein, Alexander, Talhouk, Aline, Osorio, Ana, Hartkopf, Andreas D., Brooks-Wilson, Angela, DeFazio, Anna, Fischer, Anna, Hartmann, Arndt, Hernandez, Brenda Y., McCauley, Bryan M., Karpinskyj, Chloe, de Sousa, Christiani B., Høgdall, Claus, Tiezzi, Daniel G., Herpel, Esther, Taran, Florin Andrei, Modugno, Francesmary, Keeney, Gary, Nelson, Gregg, Steed, Helen, Song, Honglin, Luk, Hugh, Benitez, Javier, Alsop, Jennifer, Koziak, Jennifer M., Lester, Jenny, Rothstein, Joseph H., de Andrade, Jurandyr M., Lundvall, Lene, Paz-Ares, Luis, Robles-Díaz, Luis, Wilkens, Lynne R., Garcia, Maria J., Intermaggio, Maria P., Alcaraz, Marie-Lyne, Brett, Mary A., Beckmann, Matthias W., Jimenez-Linan, Mercedes, Anglesio, Michael, Carney, Michael E., Schneider, Michael, Traficante, Nadia, Pejovic, Nadja, Singh, Naveena, Le, Nhu, Sinn, Peter, Ghatage, Prafull, Erber, Ramona, Edwards, Robert, Vierkant, Robert, Ness, Roberta B., Leung, Samuel, Orsulic, Sandra, Brucker, Sara Y., Kaufmann, Scott H., Fereday, Sian, Gayther, Simon, Winham, Stacey J., Kommoss, Stefan, Pejovic, Tanja, Longacre, Teri A., McGuire, Valerie, Rhenius, Valerie, Sieh, Weiva, Shvetsov, Yurii B., Whittemore, Alice S., Staebler, Annette, Karlan, Beth Y., Rodriguez-Antona, Cristina, Bowtell, David D., Goode, Ellen L., Høgdall, Estrid, Candido dos Reis, Francisco J., Gronwald, Jacek, Chang-Claude, Jenny, Moysich, Kirsten B., Kelemen, Linda E., Cook, Linda S., Goodman, Marc T., Fasching, Peter A., Crawford, Robin, Deen, Suha, Menon, Usha, Huntsman, David G., Köbel, Martin, Ramus, Susan J., Pharoah, Paul D. P., Brenton, James D.

مصطلحات موضوعية: Article, /692/4017, /692/4028/67/1517/1709

الوصف: Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

وصف الملف: application/pdf; application/zip; text/xml

العلاقة: https://www.repository.cam.ac.uk/handle/1810/324075Test

الإتاحة: https://doi.org/10.17863/CAM.71532Test
https://www.repository.cam.ac.uk/handle/1810/324075Test

المؤلفون: Chen, Minhui, Brackett, Craig M., Burdelya, Lyudmila G., Punnanitinont, Achamaporn, Patnaik, Santosh K., Matsuzaki, Junko, Odunsi, Adekunle O., Gudkov, Andrei V., Singh, Anurag K., Repasky, Elizabeth A., Gurova, Katerina V.

المساهمون: National Cancer Institute

المصدر: Cancer Immunology, Immunotherapy ; volume 70, issue 7, page 2073-2086 ; ISSN 0340-7004 1432-0851

مصطلحات موضوعية: Cancer Research, Oncology, Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.1007/s00262-020-02846-8Test

المؤلفون: Shu, ShinLa, Matsuzaki, Junko, Want, Muzamil Y., Conway, Alexis, Benjamin-Davalos, Shawna, Allen, Cheryl L., Koroleva, Marina, Battaglia, Sebastiano, Odunsi, Adekunle, Minderman, Hans, Ernstoff, Marc S.

المساهمون: National Cancer Institute, RPCI-UPCI Ovarian Cancer SPORE, The Katherine Anne Gioia Endowed Chair in Cancer Medicine, Roswell Park Comprehensive Cancer Center

المصدر: Immunological Investigations ; volume 49, issue 7, page 744-757 ; ISSN 0882-0139 1532-4311

الإتاحة: https://doi.org/10.1080/08820139.2020.1803353Test