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37 results on '"Hosoya, Hitomi"'

3. A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia

Author

Srinagesh, Hrishikesh, Jackson, Clayton, Shiraz, Parveen, Jeyakumar, Nikeshan, Hamilton, Mark, Egeler, Emily, Mavroukakis, Sharon, Kuo, Adam, Cancilla, Juancarlos, Sahaf, Bita, Agarwal, Neha, Kanegai, Alyssa, Kramer, Anne Marijn, Arai, Sally, Bharadwaj, Sushma, Dahiya, Saurabh, Hosoya, Hitomi, Johnston, Laura, Kennedy, Vanessa, Liedtke, Michaela, Lowsky, Robert, Mikkilineni, Lekha, Negrin, Robert, Rezvani, Andrew, Sidana, Surbhi, Shizuru, Judith, Smith, Melody, Weng, Wen-Kai, Feldman, Steven, Frank, Matthew J., Lee, Zachary, Tagliaferri, Mary, Marcondes, A. Mario, Miklos, David, Mackall, Crystal, and Muffly, Lori

Published
2024
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4. Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma

Author

Logue, Jennifer M., Peres, Lauren C., Hashmi, Hamza, Colin-Leitzinger, Christelle M., Shrewsbury, Alexandria M., Hosoya, Hitomi, Gonzalez, Rebecca M., Copponex, Christina, Kottra, Krista H., Hovanky, Vanna, Sahaf, Bita, Patil, Sunita, Lazaryan, Aleksandr, Jain, Michael D., Baluch, Aliyah, Klinkova, Olga V., Bejanyan, Nelli, Faramand, Rawan G., Elmariah, Hany, Khimani, Farhad, Davila, Marco L., Mishra, Asmita, Blue, Brandon J., Grajales-Cruz, Ariel F., Castaneda Puglianini, Omar A., Liu, Hien D., Nishihori, Taiga, Freeman, Ciara L., Brayer, Jason B., Shain, Kenneth H., Baz, Rachid C., Locke, Frederick L., Alsina, Melissa, Sidana, Surbhi, and Hansen, Doris K.

Published
2022
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6. PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3

Author

Salameh, Ahmad, Lee, Alessandro K, Cardó-Vila, Marina, Nunes, Diana N, Efstathiou, Eleni, Staquicini, Fernanda I, Dobroff, Andrey S, Marchiò, Serena, Navone, Nora M, Hosoya, Hitomi, Lauer, Richard C, Wen, Sijin, Salmeron, Carolina C, Hoang, Anh, Newsham, Irene, Lima, Leandro A, Carraro, Dirce M, Oliviero, Salvatore, Kolonin, Mikhail G, Sidman, Richard L, Do, Kim-Anh, Troncoso, Patricia, Logothetis, Christopher J, Brentani, Ricardo R, Calin, George A, Cavenee, Webster K, Dias-Neto, Emmanuel, Pasqualini, Renata, and Arap, Wadih

Subjects
Aging, Genetics, Prostate Cancer, Biotechnology, Cancer, Urologic Diseases, 2.1 Biological and endogenous factors, Aetiology, Adenosine Deaminase, Animals, Antigens, Neoplasm, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, HEK293 Cells, HeLa Cells, Humans, Immunoblotting, Introns, MCF-7 Cells, Male, Mice, SCID, Molecular Sequence Data, Neoplasm Proteins, Prostatic Neoplasms, Protein Binding, RNA Interference, RNA Precursors, RNA, Long Noncoding, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Xenograft Model Antitumor Assays, PRUNE2, PCA3, long noncoding RNA, ADAR, prostate cancer, Hela Cells
Abstract

Prostate cancer antigen 3 (PCA3) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2, a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing. PRUNE2 expression or silencing in prostate cancer cells decreased and increased cell proliferation, respectively. Moreover, PRUNE2 and PCA3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and RNA editing of PRUNE2 and PCA3 were confirmed in human prostate cancer specimens, supporting the medical relevance of our findings. These results establish PCA3 as a dominant-negative oncogene and PRUNE2 as an unrecognized tumor suppressor gene in human prostate cancer, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.

Published
2015

8. Abstract 5707: Tumor and immune determinants of response to anti-BCMA CAR T-cell therapy in multiple myeloma using cell-free DNA

Author

Carleton, Mia, primary, Hosoya, Hitomi, additional, Tanaka, Kailee L., additional, Sworder, Brian, additional, Hovanky, Vanna, additional, Sahaf, Bita, additional, Frank, Matthew J., additional, Duran, George E., additional, Zhang, Tian Y., additional, Arai, Sally, additional, Iberri, David, additional, Liedtke, Michaela, additional, Miklos, David B., additional, Khodadoust, Michael S., additional, Sidana, Surbhi, additional, and Kurtz, David M., additional

Published
2023
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9. Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM) with Renal Impairment: Real World Experience

Author

Sidana, Surbhi, primary, Peres, Lauren, additional, Hashmi, Hamza, additional, Hosoya, Hitomi, additional, Ferreri, Christopher, additional, Atrash, Shebli, additional, Khouri, Jack, additional, Voorhees, Peter M., additional, Dima, Danai, additional, Simmons, Gary Lee, additional, Kalariya, Nilesh, additional, Hovanky, Vanna, additional, Bharadwaj, Sushma, additional, Arai, Sally, additional, Miklos, David B., additional, Wagner, Charlotte, additional, Davis, James, additional, Sborov, Douglas, additional, Nishihori, Taiga, additional, Alsina, Melissa, additional, Locke, Frederick L., additional, Gonzalez, Rebecca, additional, Kocoglu, Mehmet H., additional, Sannareddy, Aishwarya, additional, Afrough, Aimaz, additional, McGuirk, Joseph P., additional, Shune, Leyla, additional, Patel, Krina K., additional, and Hansen, Doris K, additional

Published
2023
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10. Circulating Tumor DNA for Disease Characterization and Response Prediction in Myeloma Patients Undergoing Chimeric Antigen Receptor T-Cell Therapy

Author

Hosoya, Hitomi, primary, Carleton, Mia, additional, Tanaka, Kailee, additional, Sworder, Brian, additional, Hovanky, Vanna, additional, Duran, George E, additional, Zhang, Tian Y, additional, Khodadoust, Michael, additional, Miklos, David B., additional, Arai, Sally, additional, Iberri, David, additional, Liedtke, Michaela, additional, Sidana, Surbhi, additional, and Kurtz, David, additional

Published
2023
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11. Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas

Author

Sworder, Brian J., primary, Kurtz, David M., additional, Alig, Stefan K., additional, Frank, Matthew J., additional, Shukla, Navika, additional, Garofalo, Andrea, additional, Macaulay, Charles W., additional, Shahrokh Esfahani, Mohammad, additional, Olsen, Mari N., additional, Hamilton, James, additional, Hosoya, Hitomi, additional, Hamilton, Mark, additional, Spiegel, Jay Y., additional, Baird, John H., additional, Sugio, Takeshi, additional, Carleton, Mia, additional, Craig, Alexander F.M., additional, Younes, Sheren F., additional, Sahaf, Bita, additional, Sheybani, Natasha D., additional, Schroers-Martin, Joseph G., additional, Liu, Chih Long, additional, Oak, Jean S., additional, Jin, Michael C., additional, Beygi, Sara, additional, Hüttmann, Andreas, additional, Hanoun, Christine, additional, Dührsen, Ulrich, additional, Westin, Jason R., additional, Khodadoust, Michael S., additional, Natkunam, Yasodha, additional, Majzner, Robbie G., additional, Mackall, Crystal L., additional, Diehn, Maximilian, additional, Miklos, David B., additional, and Alizadeh, Ash A., additional

Published
2023
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13. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

Author

Hosoya, Hitomi, Dobroff, Andrey S., Driessen, Wouter H. P., Cristini, Vittorio, Brinker, Lina M., Staquicini, Fernanda I., Cardó-Vila, Marina, D’Angelo, Sara, Ferrara, Fortunato, Proneth, Bettina, Lin, Yu-Shen, Dunphy, Darren R., Dogra, Prashant, Melancon, Marites P., Stafford, R. Jason, Miyazono, Kohei, Gelovani, Juri G., Kataoka, Kazunori, Brinker, C. Jeffrey, Sidman, Richard L., Arap, Wadih, and Pasqualini, Renata

Published
2016

14. Determinants of Resistance to Engineered T-Cell Therapies Targeting CD19 in Large B-Cell Lymphomas

Author

Sworder, Brian, primary, Kurtz, David M., additional, Alig, Stefan K., additional, Frank, Matthew J, additional, Shukla, Navika D., additional, Garofalo, Andrea, additional, Macaulay, Charles, additional, Shahrokh Esfahani, Mohammad, additional, Olsen, Mari, additional, Hamilton, James, additional, Hosoya, Hitomi, additional, Hamilton, Mark P, additional, Spiegel, Jay Y., additional, Baird, John H., additional, Carleton, Mia, additional, Craig, Alexander F.M., additional, Younes, Sheren F., additional, Sahaf, Bita, additional, Sheybani, Natasha, additional, Schroers-Martin, Joseph, additional, Liu, Chih Long, additional, Oak, Jean S, additional, Jin, Michael C., additional, Beygi, Sara, additional, Hüttmann, Andreas, additional, Hanoun, Christine, additional, Dührsen, Ulrich, additional, Westin, Jason, additional, Khodadoust, Michael S., additional, Natkunam, Yasodha, additional, Majzner, Robbie G., additional, Mackall, Crystal L., additional, Diehn, Maximilian, additional, Miklos, David B., additional, and Alizadeh, Ash A., additional

Published
2022
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15. Accurate Detection of Clinically Actionable Copy Number Variants in Diverse Hematological Neoplasms By Routine Targeted Sequencing: A Comparative Performance Study

Author

Palomino Mosquera, Alicia, primary, Hosoya, Hitomi, additional, Jin, Michael C., additional, Shahrokh Esfahani, Mohammad, additional, Schroers-Martin, Joseph, additional, Sworder, Brian, additional, Liu, Chih Long, additional, Spiteri, Elizabeth, additional, Natkunam, Yasodha, additional, Zehnder, James L, additional, Stehr, Henning, additional, Kurtz, David M., additional, and Alizadeh, Ash A., additional

Published
2022
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16. Disease Characterization and Response Prediction in Myeloma Patients Undergoing Conventional and Cellular Therapies from Circulating Tumor DNA

Author

Hosoya, Hitomi, primary, Carleton, Mia, additional, Tanaka, Kailee L, additional, Sworder, Brian, additional, Hovanky, Vanna, additional, Duran, George E, additional, Zhang, Tian Y., additional, Khodadoust, Michael S., additional, Miklos, David B., additional, Arai, Sally, additional, Iberri, David, additional, Liedtke, Michaela, additional, Sidana, Surbhi, additional, and Kurtz, David M., additional

Published
2022
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17. Idecabtagene Vicleucel Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma with Renal Insufficiency: Real World Experience

Author

Sidana, Surbhi, primary, Peres, Lauren C., additional, Hashmi, Hamza, additional, Hosoya, Hitomi, additional, Ferreri, Christopher J., additional, Atrash, Shebli, additional, Khouri, Jack, additional, Voorhees, Peter M., additional, Dima, Danai, additional, Simmons, Gary, additional, Kalariya, Nilesh, additional, Hovanky, Vanna, additional, Bharadwaj, Sushma, additional, Arai, Sally, additional, Miklos, David B., additional, Wagner, Charlotte B, additional, Davis, James, additional, Sborov, Douglas W., additional, Nishihori, Taiga, additional, Alsina, Melissa, additional, Locke, Frederick L., additional, Gonzalez, Rebecca, additional, Kocoglu, M. Hakan, additional, Sannareddy, Aishwarya, additional, Afrough, Aimaz, additional, McGuirk, Joseph P., additional, Shune, Leyla O., additional, Patel, Krina, additional, and Hansen, Doris K., additional

Published
2022
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20. Mgta-145 + Plerixafor Provides GCSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study

Author

Sidana, Surbhi, primary, Bankova, Andriyana K., additional, Hosoya, Hitomi, additional, Kumar, Shaji, additional, Tamaresis, John, additional, Le, Anne, additional, Muffly, Lori, additional, Johnston, Laura, additional, Arai, Sally, additional, Lowsky, Robert, additional, Meyer, Everett H., additional, Rezvani, Andrew R., additional, Weng, Wen-Kai, additional, Frank, Matthew J., additional, Shiraz, Parveen, additional, Girgenti, Douglas, additional, Goncalves, Kevin A., additional, Schmelmer, Veit, additional, Davis, John, additional, Lu, Ying, additional, Shizuru, Judith A., additional, and Miklos, David B., additional

Published
2022
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22. Mgta-145 + Plerixafor Provides GCSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study

Author

Sidana, Surbhi, primary, Bankova, Andriyana K, additional, Hosoya, Hitomi, additional, Kumar, Shaji, additional, Tamaresis, John, additional, Le, Anne, additional, Muffly, Lori, additional, Johnston, Laura J., additional, Arai, Sally, additional, Lowsky, Robert, additional, Meyer, Everett H, additional, Rezvani, Andrew R., additional, Weng, Wen-Kai, additional, Frank, Matthew J., additional, Shiraz, Parveen, additional, Girgenti, Douglas, additional, Goncalves, Kevin A., additional, Schmelmer, Veit, additional, Davis, John C., additional, Lu, Ying, additional, Shizuru, Judith A, additional, and Miklos, David B., additional

Published
2021
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23. Phase 2 study of MGTA-145 + plerixafor for rapid and reliable hematopoietic stem cell (HSC) mobilization for autologous transplant in multiple myeloma.

Author

Sidana, Surbhi, primary, Bankova, Andriyana, additional, Hosoya, Hitomi, additional, Muffly, Lori S., additional, Kumar, Shaji, additional, Johnston, Laura J., additional, Lowsky, Robert, additional, Meyer, Everett, additional, Rezvani, Andrew, additional, Weng, Wen-Kai, additional, Arai, Sally, additional, Frank, Matthew Joshua, additional, Shiraz, Parveen, additional, Howell, Haley, additional, Goncalves, Kevin A, additional, Schmelmer, Veit, additional, Davis, John, additional, Shizuru, Judith, additional, and Miklos, David Bernard, additional

Published
2021
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24. 42 - Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM) with Renal Impairment: Real World Experience

Author

Sidana, Surbhi, Peres, Lauren, Hashmi, Hamza, Hosoya, Hitomi, Ferreri, Christopher, Atrash, Shebli, Khouri, Jack, Voorhees, Peter M., Dima, Danai, Simmons, Gary Lee, Kalariya, Nilesh, Hovanky, Vanna, Bharadwaj, Sushma, Arai, Sally, Miklos, David B., Wagner, Charlotte, Davis, James, Sborov, Douglas, Nishihori, Taiga, Alsina, Melissa, Locke, Frederick L., Gonzalez, Rebecca, Kocoglu, Mehmet H., Sannareddy, Aishwarya, Afrough, Aimaz, McGuirk, Joseph P., Shune, Leyla, Patel, Krina K., and Hansen, Doris K

Published
2023
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26. 85 - Mgta-145 + Plerixafor Provides GCSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study

Author

Sidana, Surbhi, Bankova, Andriyana K., Hosoya, Hitomi, Kumar, Shaji, Tamaresis, John, Le, Anne, Muffly, Lori, Johnston, Laura, Arai, Sally, Lowsky, Robert, Meyer, Everett H., Rezvani, Andrew R., Weng, Wen-Kai, Frank, Matthew J., Shiraz, Parveen, Girgenti, Douglas, Goncalves, Kevin A., Schmelmer, Veit, Davis, John, Lu, Ying, Shizuru, Judith A., and Miklos, David B.

Published
2022
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29. A Pilot Study of FDG-PET/CT in Polycythemia Vera Using Global Analysis Techniques.

Author

Ayubcha, Cyrus, Hosoya, Hitomi, Seraj, Siavash Mehdizadeh, Zadeh, Mahdi, Werner, M. S. E. Thomas, and Alavi, Abass

Subjects
*POLYCYTHEMIA vera, *GLOBAL analysis (Mathematics), *PILOT projects, *BONE marrow, *FEMUR neck, *SPLANCHNIC nerves, *BONE density
Abstract

Objective(s): Functional imaging presents a non-invasive process that may capture the hyper-metabolic nature of red bone marrow in myeloproliferative neoplasms, such as polycythemia vera (PV). Methods: This study analyzed the FDG-PET/CT scans (n=12) of six patients diagnosed with PV and six age-sex matched controls using a quantitative global analysis methodology. Results: All PV patients had elevated activities in the bone marrow of each skeletal structure as compared to matched controls with respect to mean standardized uptake value (femoral neck p=0.01, lumbar spine p=0.02, pelvis p=0.002, sternum p=0.04). Notable variations in splenic uptake were observed among the treated and untreated PV patients. Conclusion: Our study exemplifies the potential utility of PET in reflecting hyperactive bone marrow activity related to PV. Future studies may further substantiate and elaborate on the use of PET-derived metabolic data in PV. [ABSTRACT FROM AUTHOR]

Published
2020
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32. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

Author

Miyazono, Kohei, Kataok, Kazunori, Hosoya, Hitomi, D'Angelo, Sara, Ferrara, Fortunato, Yu-Shen Lin, Dunphy, Darren R., Melancon, Marites P., Stafford, R. Jason, Gelovani, Juri G., Sidman, Richard L., Brinker, C. Jeffrey, Arap, Wadih, Dobroff, Andrey S., Brinker, Lina M., Staquicini, Fernanda I., Cardó-Vila, Marina, Dogra, Prashant, Pasqualini, Renata, and Proneth, Bettina

Subjects
RECEPTOR-ligand complexes, IMAGING of cancer, DRUG delivery systems, NANOTECHNOLOGY, MATHEMATICAL models, NANOPARTICLES, BACTERIOPHAGES, LIPOSOMES
Abstract

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogelbased nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we showa broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical application.s [ABSTRACT FROM AUTHOR]

Published
2016
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33. Combinatorial targeting and discovery of ligand-receptors in organelles of mammalian cells

Author

Rangel, Roberto, primary, Guzman-Rojas, Liliana, additional, le Roux, Lucia G., additional, Staquicini, Fernanda I., additional, Hosoya, Hitomi, additional, Barbu, E. Magda, additional, Ozawa, Michael G., additional, Nie, Jing, additional, Jr, Kenneth Dunner, additional, Langley, Robert R., additional, Sage, E. Helene, additional, Koivunen, Erkki, additional, Gelovani, Juri G., additional, Lobb, Roy R., additional, Sidman, Richard L., additional, Pasqualini, Renata, additional, and Arap, Wadih, additional

Published
2012
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34. Engineering fibrotic tissue in pancreatic cancer: A novel three-dimensional model to investigate nanoparticle delivery

Author

Hosoya, Hitomi, primary, Kadowaki, Koji, additional, Matsusaki, Michiya, additional, Cabral, Horacio, additional, Nishihara, Hiroshi, additional, Ijichi, Hideaki, additional, Koike, Kazuhiko, additional, Kataoka, Kazunori, additional, Miyazono, Kohei, additional, Akashi, Mitsuru, additional, and Kano, Mitsunobu R., additional

Published
2012
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35. Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.

Author

Sidana S, Peres LC, Hashmi H, Hosoya H, Ferreri C, Khouri J, Dima D, Atrash S, Voorhees P, Simmons G, Sborov DW, Kalariya N, Hovanky V, Bharadwaj S, Miklos D, Wagner C, Kocoglu MH, Kaur G, Davis JA, Midha S, Janakiram M, Freeman C, Alsina M, Locke F, Gonzalez R, Lin Y, McGuirk J, Afrough A, Shune L, Patel KK, and Hansen DK

Subjects
Humans, Female, Male, Immunotherapy, Adoptive adverse effects, Cell- and Tissue-Based Therapy, Receptors, Chimeric Antigen, Multiple Myeloma complications, Multiple Myeloma therapy, Neoplasms, Plasma Cell, Cytopenia, Renal Insufficiency
Abstract

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl) <50 mL/min. CrCl of <30 mL/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13%) patients with RI, including 11 patients severe RI (dialysis, N=1). Patients with RI were older, more likely to be female and had higher likelihood of having Revised International Staging System stage 3 disease. Rates and severity of cytokine release syndrome (89% vs. 84%, grade ≥3: 7% vs. 2%) and immune effector cell-associated neurotoxicity syndrome (23% vs. 20%) were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term grade ≥3 cytopenias, although cytopenias were similar by 3 months following CAR T-cell therapy. Renal function did not worsen after CAR T-cell therapy in patients with RI. Response rates (93% vs. 82%) and survival outcomes (median progression-free survival: 9 vs. 8 months; P=0.26) were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.

Published
2024
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36. Embracing Myeloma Chimeric Antigen Receptor-T: From Scientific Design to Clinical Impact.

Author

Hosoya H, Rodriguez-Otero P, Sidana S, and Borrello IM

Subjects
Humans, Immunotherapy, Adoptive, Cytokines, Europe, Multiple Myeloma therapy, Receptors, Chimeric Antigen genetics
Abstract

Despite recent advancement of treatment strategies in multiple myeloma (MM), patients with relapsed/refractory MM disease, particularly after triple-class refractoriness, continue to have poor prognosis. Chimeric antigen receptor (CAR-T) cells were developed and applied to improve outcomes in this setting, and two products, idecabtagene vicleucel and ciltacabtagene autoleucel, both targeting B-cell maturation antigen, have been approved by the Food and Drug Administration in the United States and European Medicines Agency in Europe. Both have shown unprecedented clinical outcomes with high response rate and prolonged progression-free survival and overall survival in this patient population with grim prognosis. Currently, further investigations are ongoing for CAR-T targeting different tumor antigens such as G protein-coupled receptor, class C, group 5, member D or with different combinations of intracellular signaling domains, as well as fourth-generation CAR-T with antigen-unrestricted inducible cytokines. Although CAR-T therapies hold hopes and enthusiasm from the myeloma community, several hurdles remain before these treatments become available for all patients in need. These barriers include CAR-T-cell manufacturing availability, access to administering centers, financial cost, caregivers' availability, and socioeconomic and racial disparities. Expanding clinical trial eligibility criteria and real-world data collection and analysis is crucial to understand the efficacy and safety of CAR-T in the patient cohort who tends to be excluded from current trials.

Published
2023
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37. The role of 18 F-FDG PET in the assessment of a benign hematological disorder: polycythemia.

Author

Ayubcha C, Hosoya H, Seraj SM, Zadeh MZ, Werner T, and Alavi A

Subjects
Fluorodeoxyglucose F18, Humans, Radiopharmaceuticals, Polycythemia diagnostic imaging, Positron-Emission Tomography
Abstract

Fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) imaging was conceived in the early 1970 by investigators at the University of Pennsylvania as a research technique to measure brain metabolism and function by employing a non-invasive imaging approach. Soon after the introduction of whole-body PET instruments, 18 F-FDG was utilized in the assessment of a variety of solid tumors and certain hematological malignancies. Yet, the role of 18 F-FDG in assessing benign and uncommon malignant disorders of the bone marrow has not been investigated to a great extent. Fluorine-18-FDG as a molecular probe has the proven capacity to reflect the abnormal glycolytic activities inherent to a variety of disorders, where such information may serve as a guide to the clinical course of the respective disease. Recent efforts have studied bone marrow and extra-medullary disease activity in certain malignancies like chronic lymphocytic leukemia. Nonetheless, few studies have explored the role of 18 F-FDG in assessing the metabolic basis of benign disorders of red marrow. Moreover, the introduction of novel imaging analysis schemes in recent years has allowed for the global assessment of red marrow disease, which can provide a superior means for characterizing the systemic nature and burden of these disorders. Accordingly, semi-quantitative global analysis techniques as applied to the skeletal structures in 18 F-FDG PET may provide a tool to better understand these complex marrow abnormalities. Functional imaging of red bone marrow may also reveal critical information specifically regarding the extra-medullary extension of such hematological disorders that cannot be assessed by other diagnostic or imaging techniques. Myleoproliferative neoplasms (MPN) are an apt category of hematological disease that confer significantly altered systemic metabolic rates of hematopoietic stem cells (HSC) in the marrow, as such they are primed for exploration with 18 F-FDG PET. The hallmark of such disorders involves the excess production of particular cellular components in blood. After a period of excess production, scar tissue may develop in place of the HSC leading to myleofibrosis and decreased hematopoietic activity. One of the least studied disorders within the larger category of MPN with respect to the nuclear medicine is polycythemia. Polycythemia may be either primary, polycythemia vera (PV), or secondary. PV involves a JAK2+ in HSC which allows for the excessive proliferation of immature erythrocytes and depressed erythropoietin levels as a result. Secondary polycythemia occurs in response to decreased oxygen intake, often as a result of smoking, which results in increased erythropoietin and hematocrit levels. Primary and secondary polycythemia lead to an increase in overall red marrow activity and a diffusion of active red marrow into the appendicular skeleton. Clinical presentation often includes redness or irritation of the skin along with headache, fatigue and excessive bleeding. Based upon the mentioned precedent, it is evident that PET imaging with 18 F-FDG and other tracers will play a meaningful role in assessing diffuse bone marrow disorders such as hematological malignancies and myeloproliferative abnormalities. Semi-quantification studies of global bone marrow activity in such an application will be a vital means in accurately assessing the systematic nature and global burden of such benign hematological disorders such a polycythemia. Accordingly, the derived metabolic data projects to be a useful tool in the prospective clinical and scientific aspects of the diagnosis of these benign hematological disorders and the assessment of disease progression in light of relevant biological treatments. Given the nature of the disease and the enumerated capabilities of 18 F-FDG PET it is expected that one would be able to capture the systematic abnormalities inherent to the disease. Moreover, the handful of case studies supports this possibility. Three case studies have all illustrated diffuse elevated 18 F-FDG uptake throughout the axial and appendicular skeleton that reflects the hyper-metabolic red bone marrow as related to polycythemia. Moreover, the use of various functional imaging tracers, in addition to 18 F-FDG, may indirectly reflect hypermetabolism in red bone marrow through abnormal tracer accumulation in the skeletons of patients. The whole body 18 F-FDG scan of a JAK2+ PV patient before treatment (a) as compared to a matched subject (b) is found below; of note is the PV patient's elevated uptake in the pelvis, femur and spine.

Published
2019
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