Faculty Opinions recommendation of Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes.

Author(s):  
Arthur Hurwitz ◽  
Dhan Chand
Science ◽  
2018 ◽  
Vol 359 (6379) ◽  
pp. 1037-1042 ◽  
Author(s):  
Jonathan T. Sockolosky ◽  
Eleonora Trotta ◽  
Giulia Parisi ◽  
Lora Picton ◽  
Leon L. Su ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1797
Author(s):  
May C. I. van Schalkwyk ◽  
Sjoukje J. C. van der Stegen ◽  
Leticia Bosshard-Carter ◽  
Helen Graves ◽  
Sophie Papa ◽  
...  

Adoptive cancer immunotherapy using chimeric antigen receptor (CAR) engineered T-cells holds great promise, although several obstacles hinder the efficient generation of cell products under good manufacturing practice (GMP). Patients are often immune compromised, rendering it challenging to produce sufficient numbers of gene-modified cells. Manufacturing protocols are labour intensive and frequently involve one or more open processing steps, leading to increased risk of contamination. We set out to develop a simplified process to generate autologous gamma retrovirus-transduced T-cells for clinical evaluation in patients with head and neck cancer. T-cells were engineered to co-express a panErbB-specific CAR (T1E28z) and a chimeric cytokine receptor (4αβ) that permits their selective expansion in response to interleukin (IL)-4. Using peripheral blood as starting material, sterile culture procedures were conducted in gas-permeable bags under static conditions. Pre-aliquoted medium and cytokines, bespoke connector devices and sterile welding/sealing were used to maximise the use of closed manufacturing steps. Reproducible IL-4-dependent expansion and enrichment of CAR-engineered T-cells under GMP was achieved, both from patients and healthy donors. We also describe the development and approach taken to validate a panel of monitoring and critical release assays, which provide objective data on cell product quality.


2020 ◽  
Vol 20 ◽  
Author(s):  
Suman K Ray ◽  
Yamini Meshram ◽  
Sukhes Mukherjee

: Cancer immunotherapy endeavours in harnessing delicate strength and specificity of immune system for therapy of different malignancies including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies including colorectal carcinoma in a recent decade. Despite considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing-Zhou Hou ◽  
Jing Christine Ye ◽  
Jeffrey J. Pu ◽  
Hongtao Liu ◽  
Wei Ding ◽  
...  

AbstractAntibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, “off-the-shelf” universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting. Major developments and updates for the therapy of hematological malignancies were delineated at the recent Winter Symposium and New York Oncology Forum from the Chinese American Hematologist and Oncologist Network (CAHON.org). This study summarized the latest updates on novel agents and regimens for hematological malignancies from the 2020 ASH annual meeting.


Blood ◽  
2013 ◽  
Vol 122 (8) ◽  
pp. 1399-1410 ◽  
Author(s):  
Daniel Abate-Daga ◽  
Ken-ichi Hanada ◽  
Jeremy L. Davis ◽  
James C. Yang ◽  
Steven A. Rosenberg ◽  
...  

Key Points Gene expression in TCR-engineered cells resembles that of virus-reactive cells more than native tumor antigen-reactive cells. Persisting TCR gene–engineered T cells are sensitive to PD-L1–PD-1 interaction but CD160-associated impairment is ligand-independent.


2012 ◽  
Vol 31 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Christopher C Kloss ◽  
Maud Condomines ◽  
Marc Cartellieri ◽  
Michael Bachmann ◽  
Michel Sadelain

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. 34-35
Author(s):  
Maksim Mamonkin ◽  
Malcolm K. Brenner
Keyword(s):  
T Cells ◽  

2021 ◽  
Author(s):  
Moataz Dowaidar

T cells following genome editing and transformation might be detectable in peripheral blood and tumor tissues for a long time, even more than a year. The types and diversity of T-cells in peripheral blood and tumor tissues changed following transfusion of genetically modified T-cells, and some highly suspected T-cells targeting cancer cells grew, increasing the proportion of such cells. Moreover, after getting genetically engineered T cells, anticancer cytokine secretion increased. T cells changed by gene editing have certain functions, at least from an immunological standpoint. The first clinical research using the CRISPR–Cas9 gene editing method for cancer resistance is more complicated: Using CRISPR–Cas9 gene editing technology to concurrently knock out, amplify, activate and reinfuse three genes in human immune cells. This therapeutic strategy is more demanding, because the changed immune cells have a wider target scope. The data suggest that the efficacy of gene editing in immune cells was 15–45%, and the modified cells could survive long in the peripheral blood and tumor tissues of patients. After three or four months, some T-cells became central T-cells. These encouraging findings pave the way for future experimental cancer research utilizing CRISPR technology.


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