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This month in CAR-T research


Welcome to the second CAR-T Grease Monkeys newsletter, especially to the 49 new grease monkeys who signed up last month. Here’s what’s been moving the last month in CAR-T research: on the (clinical) race track, in the (preclinical) garage, and whats been overheard at the (review) shop.

Happy reading, 
Mike

News from the race track
 
1. Phase 1 trial: CD19-specific CAR-T directly after autologous stem cell transplantation can result in severe neurotoxicity and limited persistence of CAR-T cells:
CD19 CAR T Cells Following Autologous Transplantation in Poor Risk Relapsed and Refractory B cell non-Hodgkin Lymphoma.
Blood. 2019 Jul 1.
 
2. Prospective study of neurotoxicity following CD19-specific CAR-T:
Glial injury in neurotoxicity after pediatric CD19-directed chimeric antigen receptor T cell therapy.
Ann Neurol. 2019 Jul.
 
3. CD19-specific CAR-Ts in patients with CNS-involvement safe:
Tisagenlecleucel CAR-T Cell Therapy in Secondary CNS Lymphoma.
Blood. 2019 Jul 18.
 
4. Assessment of CAR-T therapy as bridging to allogeneic stem cell transplantation:
Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial.
Am J Hematol. 2019 Jul 18.
 
5. Case-report: Coagulopathy as a serious side-effect to CAR-T:
Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy
Ann Hematol., 2019 Jul;98(7).

6. Case-report: Abscopal response in patient receiving radiotherapy after BCMA-specific CAR-T:
BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy.
Cancer Immunol Res. 2019 Jul.

7. Case-report: rapidly and enormous cervical lymph node following CD19-specific CAR-T:
Severe dyspnea caused by rapid enlargement of cervical lymph node in a relapsed/refractory B-cell lymphoma patient following chimeric antigen receptor T-cell therapy.
Bone Marrow Transplant. 2019 Jul.
 
8. What freezing does to the goods:
Effect of Cryopreservation on Autologous Chimeric Antigen Receptor T Cell Characteristics.
Mol Ther. 2019 Jul 3.
 
News from the garage

9. Albumin-binding phospholipid polymers can boost CAR-T responses in mouse model:
Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor.
Science. 2019 Jul 12.

10. EGFRvIII-specific CAR-T expressing EGFR/CD3-bispecific antibodies leads to activation of endogenous T-cell and elimination of tumours in mouse model:
CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity.
Nat Biotechnol. 2019 Jul 22.

11. GPC3-specific CAR-T expressing IL-12 boost function in mouse model:
Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3-Targeted Chimeric Antigen Receptor-Engineered T Cells in Hepatocellular Carcinoma.
J Immunol. 2019 Jul 1.

12. Stronger intracellular signalling can enable the use of low affinity CARs:
Combined CD28 and 4-1BB Costimulation Potentiates Affinity-tuned Chimeric Antigen Receptor–engineered T Cells.
Clin Cancer Res. 2019 Jul 1.

13. Using a tyrosine kinase inhibitor to switch off CAR-T reduced adverse effects in mouse model:
The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells.
Sci Transl Med. 2019 Jul 3.

14. CAR-Ts need a proper engine to function:
Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy.
Blood. 2019 Jul 4.

15. CAR-T expression controlled by viral proteases, protease-inhibitors and degradation-tags in vitro:
Modulation of chimeric antigen receptor surface expression by a small molecule switch.
BMC Biotechnol. 2019 Jul 3.

16. CAR-Ts labelled with PSMA can be tracked using standard PET radioligands:
Imaging CAR T cell therapy with PSMA-targeted positron emission tomography.
Sci Adv. 2019 Jul 3.

17. CAIX-specific CAR-Ts might be option against glioblastoma:
Targeting Hypoxia Downstream Signaling Protein, CAIX, for CAR-T Cell Therapy against Glioblastoma.
Neuro Oncol. 2019 Jul 4.

18. CD19-specific CARs kill myeloma cells because there’s (a very small amount of) CD19 on them:
Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T.
Nat Commun. 2019 Jul 17.

19. Anti-CD26 CAR-Ts kill each other and do not work:
T cells expressing CD26-specific chimeric antigen receptors exhibit extensive self-antigen-driven fratricide.
Immunopharmacol Immunotoxicol. 2019 Jul 15.

20. Co-culturing CAR-Ts with TGFb leads to accumulation of central memory T cells:
TGFβ Programs Central Memory Differentiation in Ex Vivo-Stimulated Human T Cells.
Cancer Immunol Res. 2019 Jul 15.

Overheard at the shop

21. Pharmacology of chimeric antigen receptor T-cells:
Chimeric antigen receptor T-cell therapy: Foundational science and clinical knowledge for pharmacy practice.
J Oncol Pharm Pract. 2019 Jul;25(5).

CARs in the news

22. The promise and price of cellular therapies, Siddhartha Mukherjee, The New Yorker, on the story of CAR-Ts.
 
23. War in the Blood, a documentary following two patients involved in first in human trials at University College London, are getting rave reviews.
Our mailing address is:
Departement of clinical
OUH, J.B. Winsløws vej 4
Odense 5000
Denmark

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Departement of clinical · OUH, J.B. Winsløws vej 4 · Odense 5000 · Denmark

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