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This month in CAR-T research


Welcome to the CAR-T Grease Monkeys newsletter #6. Here is the latest in chimeric antigen receptor research from January 2020.

Happy reading, 
Mike

News from the race track

1. Tumor-sculpting by CD19-specific CAR T-cells in ALL
Impaired death receptor signaling in leukemia causes antigen-independent resistance by inducing CAR T cell dysfunction.
Cancer Discov. 2020 Jan 30

2. Phase I: humanization of scFv and use of CD8a transmembrane region decrease side-effects 
Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma.
Nat Med. 2020 Jan 20

3. Case series: kidney injurt following CD19-specific CAR T-cell therapy 
Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Diffuse Large B-Cell Lymphoma.
Am J Kidney Dis. 2020 Jan 20

4. Case: toxoplasmosis and death following CD19-specific therapy
Disseminated toxoplasmosis and haemophagocytic lymphohistiocytosis following chimeric antigen receptor T-cell therapy.
Br J Haematol. 2020 Jan 20

News from the garage

5. Vaccine boosts claudin-specific CAR T in immuncompetent mice
An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors.
Science. 2020 Jan 24

6. Examination of CD28 and 4-1BB signaling in T cells 
THEMIS-SHP1 Recruitment by 4-1BB Tunes LCK-Mediated Priming of Chimeric Antigen Receptor-Redirected T Cells.
Cancer Cell. 2020 Jan 22

7. Why use two, when one is enough? Targeting BCMA using only a heavy-chain
Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains.
Nat Commun. 2020 Jan 15

8. CARs from central memory subset show multiple behaviors in vivo
Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy.
Nat Commun. 2020 Jan 10

9. Chemokine-receptor expression enhance CAR infiltration in mouse model
CXCR2‐modified CAR‐T cells have enhanced trafficking ability that improves treatment of hepatocellular carcinoma
Eur J Immunol. 2020 Jan 24

10. BCL-2 and TCF7 up-regulated in IL15 and IL-21 co-expressing CARs
Glypican-3-specific CAR T cells co-expressing IL15 and IL21 have superior expansion and antitumor activity against hepatocellular carcinoma.
Cancer Immunol Res. 2020 Jan 17

11. Screen identifies CD13 as a target for AML
Bi-specific and Split CAR T Cells Targeting CD13 and TIM3 Eradicate Acute Myeloid Leukemia.
Blood. 2020 Jan 17

12. Mathematical model of predator–prey dynamics in GBM
Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data
J R Soc Interface. 2020 Jan

13. PTPN2 deletion enhances HER2-specific CARs in mouse model 
PTPN2 phosphatase deletion in T cells promotes anti-tumour immunity and CAR T-cell efficacy in solid tumours.
EMBO J. 2020 Jan 15

14. Good thing we have goat anti-mouse antibodies
Monitoring Allogeneic CAR-T Cells Using Flow Cytometry.
Methods Mol Biol. 2020

CAR Talk

15. CAR Targets in multiple myeloma
Current Status of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma.
Am J Clin Oncol. 2020 Jan 27

16. Can it be done?
'Off-the-shelf' allogeneic CAR T cells: development and challenges.
Nat Rev Drug Discov. 2020 Jan 3

CARs elsewhere

17. McKinsey: Driving the next wave of innovation in CAR T-cell therapies

18. Celyad, Novartis and MSKCC: What can reduce the cost of CAR-T therapy?

19. Bertrand Delsuc (twitter) reviews 2nd EBMT-EHA European CAR T Meeting

20. Interview: Are CAR T-Cell Therapies Worth the Costs?
A look back. Most clicked in last months newsletter:
 
  1. Letting academic medical centers make CAR-T drugs would save billions
  2. T-Cell Receptor Stimulation Enhances the Expansion and Function of CD19 Chimeric Antigen Receptor-Expressing T Cells.
  3. Paving New Roads for CARs.
  4. Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better?
  5. Integrated drug profiling and CRISPR screening identify essential pathways for CAR T cell cytotoxicity.
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Departement of clinical · OUH, J.B. Winsløws vej 4 · Odense 5000 · Denmark

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