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This month in CAR-T research


Welcome to the CAR-T Grease Monkeys newsletter #3: more trial data; awareness of new and long-term side-effects grows; cool new CARs from the lab; and societies from the US and Europe weigh in. Also, Donald Trump backs CAR treatment.

Happy reading, 
Mike

News from the race track

1. Phase I: Anti-CD19 CAR treatment immediately following autologous transplantation is safe:
CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. 
Blood. 2019 Aug 15.

2. Phase II: mixing anti-BCMA and anti-CD19 CARs 1:1 in 21 myeloma patients.

A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial.
Lancet Haematol. 2019 Aug 1.

3. Case report: PD-1 checkpoint therapy following anti-CD19 CAR treatment activates CAR-T and delays disease progression 64 days:
Rapid tumor regression from PD-1 inhibition after anti-CD19 chimeric antigen receptor T-cell therapy in refractory diffuse large B-cell lymphoma.
Bone Marrow Transplant. 2019 Aug 30.

4. Phase I: dose-escalation of anti-CD19 CAR in 10 patients safe but indicate CAR inhibition by TAMs:
Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma.
Clin Cancer Res. 2019 Aug 23.

5. Retrospecitive analysis: Study of 86 patients show long-term side-effects of CAR treatment to include hypogammaglobulinemia, infections, cytopenias and GvHD:
Late events after treatment with CD19-Targeted Chimeric Antigen Receptor Modified T-cells.
Biol Blood Marrow Transplant. 2019 Aug 13.

6. Case report: haemophagocytic lymphohistiocytosis as a differential diagnosis to CRS:
Haemophagocytic lymphohistiocytosis has variable time to onset following CD19 chimeric antigen receptor T cell therapy.
Br J Haematol. 2019 Aug 13.

7. Retrospective analysis: analysis of side-effects following allogenic or autologous CAR treatment:
A retrospective comparison of allogenic and autologous chimeric antigen receptor T cell therapy targeting CD19 in patients with relapsed/refractory acute lymphoblastic leukemia.
Bone Marrow Transplant. 2019 Aug.

8. Retrospecific analysis: gastrointestinal side-effects following anti-CD19 treatment occur in 15% of patients:
Gastrointestinal Adverse Events Observed After Chimeric Antigen Receptor T-Cell Therapy.
Am J Clin Oncol. 2019 Aug 30.

News from the garage

9. Dual anti-CD79B/CD19 CARs works well in mice:
Chimeric antigen receptor T cells targeting CD79b show efficacy in lymphoma with or without co-targeting CD19.
Clin Cancer Res. 2019 Aug 22.

10. CARnage! Using a CAR to eliminate another CAR to avoid toxicities:
Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells.
Cancer Immunol Immunother. 2019 Aug 14.

11. Anti-B7-H3 CARs eradicate GBM in mice up to 120 days post-treatment
B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres.
EBioMedicine. 2019 Aug 26.

12. Protocol for mRNA transduction in large-scale production: 
Clinical-Scale Production of CAR-T Cells for the Treatment of Melanoma Patients by mRNA Transfection of a CSPG4-Specific CAR under Full GMP Compliance. 
Cancers (Basel). 2019 Aug 16.

13. Anti-BCMA CARs are surprisingly enhanced by thalidomide-derivative lenalidomide in mice:
Anti-B-cell maturation antigen chimeric antigen receptor T cell function against multiple myeloma is enhanced in the presence of lenalidomide.
Mol Cancer Ther. 2019 Aug 8.

14. PD-1 knockdown in CAR T cells enhances T cell function short term but inhibits proliferation long-term:
PD-1 silencing impairs the anti-tumor function of chimeric antigen receptor modified T cells by inhibiting proliferation activity.
J Immunother Cancer. 2019 Aug 7.

15. The tyrosine kinase inhibitor midostaurin used in AML inhibits anti-CD33 CARs in vitro:
Midostaurin abrogates CD33-directed UniCAR and CD33-CD3 bispecific antibody therapy in acute myeloid leukaemia.
Br J Haematol. 2019 Sep.

Overheard at the shop

16. The Americans weigh in: when and how to treat non-Hodgkin lymphoma patients with CARs
Utilization of Chimeric Antigen Receptor (CAR) T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B cell non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.
Biol Blood Marrow Transplant. 2019 Aug 22.

17. The Europeans weigh in: should multiple myeloma patients be treated with CARs?
CAR-T cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network.
Haematologica. 2019 Aug 22.

18. How to treat hypogammaglobulinemia in CAR-treated patients:
CAR-T - and a side order of IgG, to go? - Immunoglobulin replacement in patients receiving CAR-T cell therapy.
Blood Rev. 2019 Aug 7.

19. Review of freezing methods for CAR T cells:
Preservation of cell-based immunotherapies for clinical trials.
Cytotherapy. 2019 Aug 12.

CARs in the news

A. Trump approves CAR T treatment under Medicare.
B. International Society for Cell and Gene Therapy warns against third party cryopreserving of T cells.
C. UpToDate publishes topic on CRS.
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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