Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity against CD80/CD86–Positive B Cell Malignancies

CTLA4-chimeric antigen receptor T cells were found to accumulate in tumors and are toxic to myeloid-derived suppressor cells without signs of severe GVHD and CRS in preclinical models.
[Frontiers in Immunology]
Lin, S., Cheng, L., Ye, W., Li, S., Zheng, D., Qin, L., Wu, Q., Long, Y., Lin, S., Wang, S., Huang, G., Li, P., Yao, Y., & Sun, X. (2021). Chimeric CTLA4-CD28-CD3z T Cells Potentiate Antitumor Activity Against CD80/CD86–Positive B Cell Malignancies. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.642528 Cite
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Inter- and Intra-Tumor Heterogeneity of Metastatic Prostate Cancer Determined by Digital Spatial Gene Expression Profiling

By assessing multiple discrete areas across multiple metastases, the authors found a high level of intra-patient homogeneity with respect to tumor phenotype.
[Nature Communications]
Brady, L., Kriner, M., Coleman, I., Morrissey, C., Roudier, M., True, L. D., Gulati, R., Plymate, S. R., Zhou, Z., Birditt, B., Meredith, R., Geiss, G., Hoang, M., Beechem, J., & Nelson, P. S. (2021). Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling. Nature Communications, 12(1), 1426. https://doi.org/10.1038/s41467-021-21615-4 Cite
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Beyond Conventional Immune-Checkpoint Inhibition — Novel Immunotherapies for Renal Cell Carcinoma

Using the structure provided by the well-described cancer–immunity cycle, scientists outline the key steps required for a successful antitumour immune response in the context of renal cell carcinoma, and describe the development of promising new immunotherapies within the context of this framework.
[Nature Reviews Clinical Oncology]
Braun, D. A., Bakouny, Z., Hirsch, L., Flippot, R., Van Allen, E. M., Wu, C. J., & Choueiri, T. K. (2021). Beyond conventional immune-checkpoint inhibition — novel immunotherapies for renal cell carcinoma. Nature Reviews Clinical Oncology, 1–16. https://doi.org/10.1038/s41571-020-00455-z Cite
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Cutaneous Immune-Related Adverse Events in Patients with Melanoma Treated with Checkpoint Inhibitors

Investigators review the clinical presentations of cutaneous immune‐related adverse effects associated with checkpoint inhibitor therapy in adult patients with metastatic malignant melanoma.
[British Journal of Dermatology]
Gault, A., Anderson, A. E., Plummer, R., Stewart, C., Pratt, A. G., & Rajan, N. (n.d.). Cutaneous immune-related adverse events in patients with melanoma treated with checkpoint inhibitors. British Journal of Dermatology, n/a(n/a). https://doi.org/https://doi.org/10.1111/bjd.19750 Cite
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Acetylation-Dependent Regulation of PD-L1 Nuclear Translocation Dictates the Efficacy of Anti-PD-1 Immunotherapy

Investigators report that PD-L1 translocated from the plasma membrane into the nucleus through interactions with components of the endocytosis and nucleocytoplasmic transport pathways, regulated by p300-mediated acetylation and HDAC2-dependent deacetylation of PD-L1.
[Nature Cell Biology]
Gao, Y., Nihira, N. T., Bu, X., Chu, C., Zhang, J., Kolodziejczyk, A., Fan, Y., Chan, N. T., Ma, L., Liu, J., Wang, D., Dai, X., Liu, H., Ono, M., Nakanishi, A., Inuzuka, H., North, B. J., Huang, Y.-H., Sharma, S., … Wei, W. (2020). Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nature Cell Biology, 1–12. https://doi.org/10.1038/s41556-020-0562-4 Cite
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Nanoparticle Delivery of Immunostimulatory Oligonucleotides Enhances Response to Checkpoint Inhibitor Therapeutics

Researchers found that their engineered nanoparticles carrying a CpG DNA ligand of TLR9 could suppress tumor growth in several animal models of various cancers, resulting in an abscopal effect on distant tumors, and improving responsiveness to anti-CTLA4 treatment with combinatorial effects after intratumoral administration.
[Proceedings of the National Academy of Sciences of the United States of America]
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