Integrative Bulk and Single-Cell Profiling of Pre-manufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy

The authors extensively characterized the pre manufacture T-cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy.
[Cancer Discovery]
Chen, G. M., Chen, C., Das, R. K., Gao, P., Chen, C.-H., Bandyopadhyay, S., Ding, Y.-Y., Uzun, Y., Yu, W., Zhu, Q., Myers, R. M., Grupp, S. A., Barrett, D. M., & Tan, K. (2021). Integrative bulk and single-cell profiling of pre-manufacture T-cell populations reveals factors mediating long-term persistence of CAR T-cell therapy. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-1677 Cite
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The Role of B Cells in PE Pathophysiology: A Potential Target for Perinatal Cell-Based Therapy?

The authors disscuss evidence on the ability of perinatal cells to inhibit B cell proliferation, impair B cell differentiation, and promote regulatory B cell formation.
[International Journal of Molecular Sciences]
Magatti, M., Masserdotti, A., Cargnoni, A., Papait, A., Stefani, F. R., Silini, A. R., & Parolini, O. (2021). The Role of B Cells in PE Pathophysiology: A Potential Target for Perinatal Cell-Based Therapy? International Journal of Molecular Sciences, 22(7), 3405. https://doi.org/10.3390/ijms22073405 Cite
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Temporal Multiomic Modeling Reveals a B-Cell Receptor Proliferative Program in Chronic Lymphocytic Leukemia

Using an original ex vivo model of B-cell receptor-induced proliferation of chronic lymphocytic leukemia cells, researchers generated 108 temporal transcriptional and proteomic profiles from one hour up to four days after BCR activation.
[Leukemia]
Schleiss, C., Carapito, R., Fornecker, L.-M., Muller, L., Paul, N., Tahar, O., Pichot, A., Tavian, M., Nicolae, A., Miguet, L., Mauvieux, L., Herbrecht, R., Cianferani, S., Freund, J.-N., Carapito, C., Maumy-Bertrand, M., Bahram, S., Bertrand, F., & Vallat, L. (2021). Temporal multiomic modeling reveals a B-cell receptor proliferative program in chronic lymphocytic leukemia. Leukemia, 1–12. https://doi.org/10.1038/s41375-021-01221-5 Cite
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CAR-T Cell Therapy: Current Limitations and Potential Strategies

Scientists discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
[Blood Cancer Journal]
Sterner, R. C., & Sterner, R. M. (2021). CAR-T cell therapy: current limitations and potential strategies. Blood Cancer Journal, 11(4), 1–11. https://doi.org/10.1038/s41408-021-00459-7 Cite
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Vaccination with Prefusion-Stabilized Respiratory Syncytial Virus Fusion Protein Induces Genetically and Antigenically Diverse Antibody Responses

Researchers evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages.
[Immunity]
Mukhamedova, M., Wrapp, D., Shen, C.-H., Gilman, M. S. A., Ruckwardt, T. J., Schramm, C. A., Ault, L., Chang, L., Derrien-Colemyn, A., Lucas, S. A. M., Ransier, A., Darko, S., Phung, E., Wang, L., Zhang, Y., Rush, S. A., Madan, B., Stewart-Jones, G. B. E., Costner, P. J., … Mascola, J. R. (2021). Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2021.03.004 Cite
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The Neutralizing Antibody, LY-CoV555, Protects against SARS-CoV-2 Infection in Non-human Primates

Researchers report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with COVID-19.
[Science Translational Medicine]
Jones, B. E., Brown-Augsburger, P. L., Corbett, K. S., Westendorf, K., Davies, J., Cujec, T. P., Wiethoff, C. M., Blackbourne, J. L., Heinz, B. A., Foster, D., Higgs, R. E., Balasubramaniam, D., Wang, L., Zhang, Y., Yang, E. S., Bidshahri, R., Kraft, L., Hwang, Y., Žentelis, S., … Falconer, E. (2021). The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in non-human primates. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.abf1906 Cite
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Combining Ibrutinib and Checkpoint Blockade Improves CD8+ T-Cell Function and Control of Chronic Lymphocytic Leukemia in Em-TCL1 Mice

By using the Eµ-TCL1 adoptive transfer mouse model of chronic lymphocytic leukemia, scientists observed that ibrutinib effectively controled leukemia development, but also resulted in significantly lower numbers of CD8+ effector T-cells, with lower expression of activation markers, as well as impaired proliferation and effector function.
[Haematologica]
Hanna, B. S., Yazdanparast, H., Demerdash, Y., Roessner, P. M., Schulz, R., Lichter, P., Stilgenbauer, S., & Seiffert, M. (2021). Combining ibrutinib and checkpoint blockade improves CD8+ T-cell function and control of chronic lymphocytic leukemia in Em-TCL1 mice. Haematologica, 106(4), 968–977. https://doi.org/10.3324/haematol.2019.238154 Cite
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Diffuse Large B-Cell Lymphoma: New Targets and Novel Therapies

Three CAR-T cell products are currently approved by the FDA, with others in clinical trials. Additional agents in development include bispecific antibodies and antibody drug conjugates.
[Blood Cancer Journal]
Cheson, B. D., Nowakowski, G., & Salles, G. (2021). Diffuse large B-cell lymphoma: new targets and novel therapies. Blood Cancer Journal, 11(4), 1–10. https://doi.org/10.1038/s41408-021-00456-w Cite
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BCL3 Couples Cancer Stem Cell Enrichment with Pancreatic Cancer Molecular Subtypes

Scientists demonstrated that Bcl3 impacted pancreatic carcinogenesis by restraining cancer stem cell expansion and by curtailing an aggressive and metastatic tumor burden in pancreatic ductal adenocarcinoma across species.
[Gastroenterology]
Ai, J., Wörmann, S. M., Görgülü, K., Vallespinos, M., Zagorac, S., Alcala, S., Wu, N., Kabacaoglu, D., Berninger, A., Navarro, D., Kaya-Aksoy, E., Ruess, D. A., Ciecielski, K. J., Kowalska, M., Demir, E. I., Ceyhan, G. O., Heid, I., Braren, R., Riemann, M., … Algül, H. (2021). BCL3 couples cancer stem cell enrichment with pancreatic cancer molecular subtypes. Gastroenterology, 0(0). https://doi.org/10.1053/j.gastro.2021.03.051 Cite
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Sorrento Enters Into Merger Agreement to Acquire Late-Stage Oncology Company ACEA Therapeutics

Sorrento Therapeutics, Inc. announced the signing of a merger agreement pursuant to which Sorrento will acquire ACEA Therapeutics, Inc. The acquisition will include late clinical stage drug Abivertinib, clinical stage candidate AC0058, preclinical stage candidate AC0939, and ACEA’s extensive proprietary library of small molecules, which potentially have applications for numerous human disease indications, including non-small cell lung cancer, B cell lymphomas, systemic lupus, rheumatoid arthritis, multiple sclerosis and viral infections.
[Sorrento Therapeutics, Inc. (Globe Newswire, Inc.)]
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Kite Submits Supplemental Biologics License Application to US Food and Drug Administration for Tecartus® in Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia

Kite announced that it has submitted a supplemental Biologics License Application to FDA for Tecartus® for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
[Kite (BusinessWire, Inc.)]
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