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This month in CAR-T research

Welcome to the first CAR-T Grease Monkeys newsletter. The aim is to bring you the most exciting news from CAR-T mechanics and grease monkeys around the world. 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, 

News from the race track

1. Coagulopathy as a serious side-effect to CAR-T:
Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy
Jiang H et al, Ann Hematol., 2019 Jul;98(7).

2. Neurotoxicity correlates with cytokine release syndrome and higher CAR-T cell numbers in blood:
Glial injury in neurotoxicity after pediatric CD19-directed chimeric antigen receptor T cell therapy
Gust J et al, Ann Neurol., 2019 Jul;86(1).

3. Case-report: CAR-Ts from patients brother effective but causes serious GvHD:

Haploidentical CD19/CD22 bispecific CAR-T cells induced MRD-negative remission in a patient with relapsed and refractory adult B-ALL after haploidentical hematopoietic stem cell transplantation.
Jia H et al, J Hematol Oncol. 2019 Jun,

4. Radiation therapy prior to CAR-T treatment possible, but best to wait till after apheresis:
Radiation therapy as a bridging strategy for CAR T cell therapy with axicabtagene ciloleucel in diffuse large B-cell lymphoma.
Sim AJ et al, Int J Radiat Oncol Biol Phys. 2019 Jun 5.

5. Low affinity scFv's lead to fewer side-effects:
A safe and potent anti-CD19 CAR T cell therapy.
Ying Z et al, Nature Med 2019 Jun:25(6).

News from the garage

1.  IL-12 #1: overexpressing CAR-Ts infiltrate and persist better in mouse tumour model:
Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3-Targeted Chimeric Antigen Receptor-Engineered T Cells in Hepatocellular Carcinoma.
Liu Y et al, J Immunology, 2019 Jul 1;203(1).

2. IL-12 #2: CAR-T and rIL-12 combination increases efficacy of CEA-specific CAR-Ts
Significantly increased anti-tumor activity of carcinoembryonic antigen-specific chimeric antigen receptor T cells in combination with recombinant human IL-12.
Chi X et la, Cancer Med, 2019.

3. Making CD19-negative cancer cells visible for aCD19-CAR-Ts using CD19. Confused yet?
Retargeting CD19 CAR T cells via engineered CD19-fusion proteins.
Klesmith JR, Mol Pharm. 2019 Jun 26.

4. Single-cell analysis of CAR-T's revealed mixed transcriptional programs:
Single-cell Analysis of CAR-T Cell Activation Reveals A Mixed TH1/TH2 Response Independent of Differentiation.
Xhangolli et al, Genomics Proteomics Bioinformatics. 2019 Jun 20.

5. TOX and TOX2 transcription factors involved in CAR-T exhaustion:
TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion.
Seo H et al, PNAS, 2019 Jun 19.

6. Homemade stir tank for CAR-T production:
Establishing the scalable manufacture of primary human T-cells in an automated stirred-tank bioreactor.
Biotechnol Bioeng. 2019 Jun 11.

7. Knockout of CD33 in allogenic donors for better follow-up treatment with anti-CD33 CAR-Ts:
Gene-edited stem cells enable CD33-directed immune therapy for myeloid malignancies.
Borot F et al, PNAS, 2019 Jun 11

8. Gene-editing galore to create allogenic CAR-Ts with a safety switch:
Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.
Sommer C et al, Mol Ther. 2019 Jun 5;27(6).

9. Titratration and control of CAR-Ts using small molecules in pancreatic mouse model: 
Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma.
Raj D et al, Gut, 2019 Jun;68(6).

Overheard at the shop

1. Next generation CAR-T #1:
CAR-T immunotherapies: Biotechnological strategies to improve safety, efficacy and clinical outcome through CAR engineering.
Panagopoulou TI, Rafiq QA, Biotechnol Adv. 2019 Jun 25.

2. Next generation CAR-T #2:
Gene editing for immune cell therapies.
Bailey SR and Maus MV. Nat Biotechnol. 2019 Jun 3

3. What doctors think about when they treat patients with CAR-T:
An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT.
Hayden et al, Curr Res Transl Med. 2019 Jun 8.

4. Whats up with all this CRISPR stuff anyway? Review of approaches to CAR-Ts (among other things):
Therapeutic gene editing in haematological disorders with CRISPR/Cas9.
Jensen TI et al, Br J Haematol. 2019 Jun;185(5).
Give me more news!

1. MD Anderson Cancer Center released an app called CARTOX (Apple / Google) for assessing CRS in treated patients

2. EMBT would like everybody in Europe to register CAR-T patient data and released this Q/A to explain how.  

3. And finally: ALL survivor and CAR-T patient-pioneer Emily Whitehead goes running for a good cause.

That was a lot of good stuff! Hope you enjoyed it. This is more fun if we engage with each other, so please - do get in touch with ideas, comments or just to chat about CAR-T stuff. And please tell your geeky friends to sign-up.

Best, Mike
Our mailing address is:
Departement of clinical
OUH, J.B. Winsløws vej 4
Odense 5000

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

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