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365 results on '"Czerwinski, Debra K."'

6. Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens

Author

Khodadoust, Michael S, Olsson, Niclas, Wagar, Lisa E, Haabeth, Ole AW, Chen, Binbin, Swaminathan, Kavya, Rawson, Keith, Liu, Chih Long, Steiner, David, Lund, Peder, Rao, Samhita, Zhang, Lichao, Marceau, Caleb, Stehr, Henning, Newman, Aaron M, Czerwinski, Debra K, Carlton, Victoria EH, Moorhead, Martin, Faham, Malek, Kohrt, Holbrook E, Carette, Jan, Green, Michael R, Davis, Mark M, Levy, Ronald, Elias, Joshua E, and Alizadeh, Ash A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Good Health and Well Being, Antigen Presentation, Antigens, Neoplasm, CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, DNA Mutational Analysis, Epitopes, T-Lymphocyte, Exome, Genomics, HLA-D Antigens, Histocompatibility Antigens Class I, Humans, Immunoglobulin Variable Region, Immunotherapy, Lymphoma, Mantle-Cell, Mutation, Proteomics, General Science & Technology
Abstract

Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients. Remarkably, all discovered neoantigenic peptides were exclusively derived from the lymphoma immunoglobulin heavy- or light-chain variable regions. Although we identified MHC presentation of private polymorphic germline alleles, no mutated peptides were recovered from non-immunoglobulin somatically mutated genes. Somatic mutations within the immunoglobulin variable region were almost exclusively presented by MHC class II. We isolated circulating CD4+ T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing of autologous lymphoma cells. These results demonstrate that an integrative approach combining MHC isolation, peptide identification, and exome sequencing is an effective platform to uncover tumour neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.

Published
2017

8. A clinical trial of therapeutic vaccination in lymphoma with serial tumor sampling and single cell analysis

Author

Shree, Tanaya, primary, Haebe, Sarah Elena, additional, Czerwinski, Debra K, additional, Eckhert, Erik, additional, Day, Grady, additional, Sathe, Anuja, additional, Grimes, Susan M., additional, Frank, Matthew J., additional, Maeda, Lauren, additional, Alizadeh, Ash A, additional, Advani, Ranjana H, additional, Hoppe, Richard T., additional, Long, Steven R., additional, Martin, Brock A, additional, Ozawa, Michael G., additional, Khodadoust, Michael S, additional, Ji, Hanlee P., additional, and Levy, Ronald, additional

Published
2023
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10. Imaging activated T cells predicts response to cancer vaccines

Author

Alam, Israt S., Mayer, Aaron T., Sagiv-Barfi, Idit, Wang, Kezheng, Vermesh, Ophir, Czerwinski, Debra K., Johnson, Emily M., James, Michelle L., Levy, Ronald, and Gambhir, Sanjiv S.

Subjects
Cancer treatment -- Research, Cancer vaccines -- Usage -- Research, T cells -- Analysis, Biological markers -- Research, Health care industry
Abstract

In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies. Intratumoral vaccine administration is thought to activate a T cell-mediated immune response, which begins in the treated tumor and cascades systemically. In this study, we describe a PET tracer ([sup.64]Cu-DOTA-AbOX40) that enabled noninvasive and longitudinal imaging of OX40, a cell-surface marker of T cell activation. We report the spatiotemporal dynamics of T cell activation following in situ vaccination with CpG oligodeoxynucleotide in a dual tumor-bearing mouse model. We demonstrate that OX40 imaging was able to predict tumor responses on day 9 after treatment on the basis of tumor tracer uptake on day 2, with greater accuracy than both anatomical and blood-based measurements. These studies provide key insights into global T cell activation following local CpG treatment and indicate that [sup.64]Cu-DOTA-AbOX40 is a promising candidate for monitoring clinical cancer immunotherapy strategies., Introduction The field of immuno-oncology has experienced rapid and exciting growth, benefiting from the development of intricate adoptive cell therapies (1) and numerous mAbs (with clinical approval of over 20 [...]

Published
2018
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12. Supplementary Figure from CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

Author

Shree, Tanaya, primary, Shankar, Vishnu, primary, Lohmeyer, Julian J.K., primary, Czerwinski, Debra K., primary, Schroers-Martin, Joseph G., primary, Rodriguez, Gladys M., primary, Beygi, Sara, primary, Kanegai, Alyssa M., primary, Corbelli, Karen S., primary, Gabriel, Etelka, primary, Kurtz, David M., primary, Khodadoust, Michael S., primary, Gupta, Neel K., primary, Maeda, Lauren S., primary, Advani, Ranjana H., primary, Alizadeh, Ash A., primary, and Levy, Ronald, primary

Published
2023
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13. Supplementary Data from CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

Author

Shree, Tanaya, primary, Shankar, Vishnu, primary, Lohmeyer, Julian J.K., primary, Czerwinski, Debra K., primary, Schroers-Martin, Joseph G., primary, Rodriguez, Gladys M., primary, Beygi, Sara, primary, Kanegai, Alyssa M., primary, Corbelli, Karen S., primary, Gabriel, Etelka, primary, Kurtz, David M., primary, Khodadoust, Michael S., primary, Gupta, Neel K., primary, Maeda, Lauren S., primary, Advani, Ranjana H., primary, Alizadeh, Ash A., primary, and Levy, Ronald, primary

Published
2023
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14. Data from CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

Author

Shree, Tanaya, primary, Shankar, Vishnu, primary, Lohmeyer, Julian J.K., primary, Czerwinski, Debra K., primary, Schroers-Martin, Joseph G., primary, Rodriguez, Gladys M., primary, Beygi, Sara, primary, Kanegai, Alyssa M., primary, Corbelli, Karen S., primary, Gabriel, Etelka, primary, Kurtz, David M., primary, Khodadoust, Michael S., primary, Gupta, Neel K., primary, Maeda, Lauren S., primary, Advani, Ranjana H., primary, Alizadeh, Ash A., primary, and Levy, Ronald, primary

Published
2023
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15. Data from In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma

Author

Frank, Matthew J., primary, Reagan, Patrick M., primary, Bartlett, Nancy L., primary, Gordon, Leo I., primary, Friedberg, Jonathan W., primary, Czerwinski, Debra K., primary, Long, Steven R., primary, Hoppe, Richard T., primary, Janssen, Robert, primary, Candia, Albert F., primary, Coffman, Robert L., primary, and Levy, Ronald, primary

Published
2023
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16. Supplemental Data from In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma

Author

Frank, Matthew J., primary, Reagan, Patrick M., primary, Bartlett, Nancy L., primary, Gordon, Leo I., primary, Friedberg, Jonathan W., primary, Czerwinski, Debra K., primary, Long, Steven R., primary, Hoppe, Richard T., primary, Janssen, Robert, primary, Candia, Albert F., primary, Coffman, Robert L., primary, and Levy, Ronald, primary

Published
2023
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21. Activating Immune Effectors and Dampening Immune Suppressors Generates Successful Therapeutic Cancer Vaccination in Patients with Lymphoma

Author

Shree, Tanaya, primary, Haebe, Sarah, additional, Czerwinski, Debra K., additional, Eckhert, Erik, additional, Day, Grady, additional, Sathe, Anuja, additional, Grimes, Susan M., additional, Frank, Matthew J, additional, Maeda, Lauren S., additional, Alizadeh, Ash A., additional, Advani, Ranjana H., additional, Hoppe, Richard, additional, Long, Steven R., additional, Martin, Brock, additional, Ozawa, Michael G., additional, Khodadoust, Michael S., additional, Ji, Hanlee P., additional, and Levy, Ronald, additional

Published
2022
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30. CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

Author

Shree, Tanaya, primary, Shankar, Vishnu, additional, Lohmeyer, Julian J.K., additional, Czerwinski, Debra K., additional, Schroers-Martin, Joseph G., additional, Rodriguez, Gladys M., additional, Beygi, Sara, additional, Kanegai, Alyssa M., additional, Corbelli, Karen S., additional, Gabriel, Etelka, additional, Kurtz, David M., additional, Khodadoust, Michael S., additional, Gupta, Neel K., additional, Maeda, Lauren S., additional, Advani, Ranjana H., additional, Alizadeh, Ash A., additional, and Levy, Ronald, additional

Published
2022
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32. Serial Fine Needle Aspiration (FNA) Allows Direct Sampling of Malignant and Infiltrating Immune Cells in Patients with B-cell Lymphoma Receiving Immunotherapy

Author

Mooney, Kelly L., Czerwinski, Debra K., Shree, Tanaya, Frank, Matthew J., Haebe, Sarah, Martin, Brock A., Testa, Stefano, Levy, Ronald, and Long, Steven R.

Subjects
Lymphoma, B-Cell, Neoplasms, Biopsy, Fine-Needle, Tumor Microenvironment, Humans, Immunotherapy, Lymph Nodes, Article
Abstract

BACKGROUND: Fine needle aspiration (FNA) is used to diagnose malignancies, recurrences, and metastases. The procedure is quick, well-tolerated, and can be facilitated by ultrasound guidance. METHODS: Here we describe our experience using serial FNAs to harvest cellular material during four clinical trials of immunotherapy by in situ vaccination in patients with low grade lymphoma. RESULTS: Two hundred and ninety-six FNA samples were collected from 44 patients spanning approximately six weeks for each patient. Samples were sufficient in quantity and quality to be analyzed by flow cytometry and/or single-cell mRNA sequencing. FNA samples yielded an average of 12 x 10(6) cells with a mean cellular viability of 86%. Material collected from the tumor lymph nodes differed significantly in proportions and phenotype of cellular populations compared to matched peripheral blood samples. Comparison of flow cytometry results obtained by FNA directly from the patient to that of an FNA performed ex vivo and a dissociation of the same lymph node after surgical excision confirmed that FNA sampling of the patient accurately represents the tumor and the microenvironment. Analysis of the FNA samples from immunotherapy-treated target lymph nodes vs nodes from non-treated tumor sites provided insight into the impact of specific immunotherapy regimens. CONCLUSIONS: This is the largest study describing the use of serial FNA sampling to harvest cellular material during immunotherapy clinical trials. The success of this technique opens the door for FNA sampling to expand significantly future investigation of the dynamic effects of investigational agents, be they immune therapies or targeted therapies.

Published
2021

34. Time Since Last Anti-CD20 Treatment Is a Major Determinant of Sars-Cov-2 Vaccine Response in a Large Cohort of Patients with B-Cell Lymphoma

Author

Shree, Tanaya, primary, Shankar, Vishnu, additional, Czerwinski, Debra K., additional, Rodriguez, Gladys, additional, Beygi, Sara, additional, Schroers-Martin, Joseph G, additional, Advani, Ranjana, additional, Maeda, Lauren S., additional, Gupta, Neel K., additional, Khodadoust, Michael S., additional, Kurtz, David M., additional, Corbelli, Karen S., additional, Gabriel, Etelka, additional, Kanegai, Alyssa M., additional, Alizadeh, Ash A., additional, and Levy, Ronald, additional

Published
2021
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35. Therapeutic and Immunologic Responses Elicited By in Situ Vaccination with CpG, Ibrutinib, and Low-Dose Radiation

Author

Shree, Tanaya, primary, Haebe, Sarah, additional, Czerwinski, Debra K., additional, Day, Grady, additional, Sathe, Anuja, additional, Khodadoust, Michael S., additional, Frank, Matthew J., additional, Beygi, Sara, additional, Hoppe, Richard, additional, Long, Steven R., additional, Martin, Brock, additional, Ji, Hanlee P., additional, and Levy, Ronald, additional

Published
2021
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42. An mRNA SARS-CoV-2 Vaccine Employing Charge-Altering Releasable Transporters with a TLR-9 Agonist Induces Neutralizing Antibodies and T Cell Memory

Author

Haabeth, Ole A. W., primary, Lohmeyer, Julian J. K., additional, Sallets, Adrienne, additional, Blake, Timothy R., additional, Sagiv-Barfi, Idit, additional, Czerwinski, Debra K., additional, McCarthy, Blaine, additional, Powell, Abigail E., additional, Wender, Paul A., additional, Waymouth, Robert M., additional, and Levy, Ronald, additional

Published
2021
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43. An mRNA SARS-CoV-2 vaccine employing Charge-Altering Releasable Transporters with a TLR-9 agonist induces neutralizing antibodies and T cell memory

Author

Haabeth, Ole A.W., primary, Lohmeyer, Julian J.K., additional, Sallets, Adrienne, additional, Blake, Timothy R., additional, Sagiv-Barfi, Idit, additional, Czerwinski, Debra K., additional, McCarthy, Blaine, additional, Powell, Abigail E., additional, Wender, Paul A., additional, Waymouth, Robert M., additional, and Levy, Ronald, additional

Published
2021
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44. Prediction of survival in diffuse large-B-cell lymphoma based on the expression

Author

Lossos, Izidore S., Botstein, David, Levy, Ronald, Czerwinski, Debra K., Alizadeh, Ash A., Wechser, Mark A., and Tibshirani, Rob

Subjects
Gene expression -- Usage, Lymphomas -- Diagnosis
Abstract

A study conducted on 36 genes, whose expressions had been reported to predict survival in diffuse large-B-cell lymphoma, is presented. According to the results, the measurement of six genes is sufficient to predict overall survival in diffuse large-B-cell lymphoma.

Published
2004

48. Single Cell Analysis of Serial Lymphoma Biopsies Reveals Dynamic Immune Modulation and Predictors of Response in Patients Undergoing in Situ Vaccination

Author

Shree, Tanaya, primary, Haebe, Sarah, additional, Sathe, Anuja, additional, Day, Grady, additional, Czerwinski, Debra K., additional, Lee, HoJoon, additional, Grimes, Susan, additional, Long, Steven R., additional, Martin, Brock, additional, Ji, Hanlee, additional, and Levy, Ronald, additional

Published
2020
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49. Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial

Author

Frank, Matthew J., primary, Khodadoust, Michael S., primary, Czerwinski, Debra K., primary, Haabeth, Ole A.W., primary, Chu, Michael P., primary, Miklos, David B., primary, Advani, Ranjana H., primary, Alizadeh, Ash A., primary, Gupta, Neel K., primary, Maeda, Lauren S., primary, Reddy, Sunil A., primary, Laport, Ginna G., primary, Meyer, Everett H., primary, Negrin, Robert S., primary, Rezvani, Andrew R., primary, Weng, Wen-Kai, primary, Sheehan, Kevin, primary, Faham, Malek, primary, Okada, Ami, primary, Moore, A. Holliston, primary, Phillips, Destiny L., primary, Wapnir, Irene L., primary, Brody, Joshua D., primary, and Levy, Ronald, primary

Published
2020
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50. Serial FNA allows direct sampling of malignant and infiltrating immune cells in patients with B‐cell lymphoma receiving immunotherapy.

Author

Mooney, Kelly L., Czerwinski, Debra K., Shree, Tanaya, Frank, Matthew J., Haebe, Sarah, Martin, Brock A., Testa, Stefano, Levy, Ronald, and Long, Steven R.

Abstract

Background: Fine‐needle aspiration (FNA) is used to diagnose malignancies, recurrences, and metastases. The procedure is quick and well tolerated and can be facilitated by ultrasound guidance. Methods: This article describes the authors' experience in using serial FNA to harvest cellular material during 4 clinical trials of immunotherapy by in situ vaccination in patients with low‐grade lymphoma. Results: Two hundred ninety‐six FNA samples were collected from 44 patients over a span of approximately 6 weeks for each patient. Samples were sufficient in quantity and quality to be analyzed by flow cytometry and/or single‐cell messenger RNA sequencing. FNA samples yielded an average of 12 × 106 cells with a mean cellular viability of 86%. Material collected from the tumor lymph nodes differed significantly in the proportions and phenotypes of cellular populations in comparison with matched peripheral blood samples. A comparison of flow cytometry results obtained by FNA directly from the patient and by FNA performed ex vivo and a dissociation of the same lymph node after surgical excision confirmed that FNA sampling of the patient accurately represented the tumor and the microenvironment. An analysis of the FNA samples from immunotherapy‐treated target lymph nodes versus nodes from nontreated tumor sites provided insight into the impact of specific immunotherapy regimens. Conclusions: This is the largest study describing the use of serial FNA sampling to harvest cellular material during immunotherapy clinical trials. The success of this technique opens the door for FNA sampling to expand significantly future investigations of the dynamic effects of investigational agents, be they immunotherapies or targeted therapies. Fine‐needle aspiration is a dependable method of collecting samples directly from multiple tumor nodules sequentially over the course of immunotherapy regimens. These cellular samples can then be studied and profiled to track patient responses to therapy and to study both the tumor and its microenvironment. [ABSTRACT FROM AUTHOR]

Published
2022
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