Engineered T-cell Receptor T Cells for Cancer Immunotherapy

2021 ◽  
Vol 9 (11) ◽  
pp. 1252-1261
Author(s):  
Uri Greenbaum ◽  
Ecaterina I. Dumbrava ◽  
Amadeo B. Biter ◽  
Cara L. Haymaker ◽  
David S. Hong
2018 ◽  
Vol 23 (6) ◽  
pp. 850-858.e4 ◽  
Author(s):  
Atsutaka Minagawa ◽  
Toshiaki Yoshikawa ◽  
Masaki Yasukawa ◽  
Akitsu Hotta ◽  
Mihoko Kunitomo ◽  
...  

2018 ◽  
Vol 10 (3) ◽  
pp. 203-16
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: Current cancer drugs and treatments are aiming at eradicating tumor cells, but often are more toxic then effective, killing also the normal cells and not selectively the tumor cells. There is good personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity, which called adoptive cell therapy (ACT). A review of the unique biology of T cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities.CONTENT: Chimeric antigen receptors (CAR) are recombinant receptors which provide both antigen-binding and T cell-activating functions. Many kind of CARs has been reported for the past few years, targeting an array of cell surface tumor antigens. Their biologic functions have extremely changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. The combination of CARs with costimulatory ligands, chimeric costimulatory receptors, or cytokines can be done to further enhance T cell potency, specificity and safety. CARs reflects a new class of drugs with exciting potential for cancer immunotherapy.SUMMARY: CAR-T cells have been arising as a new modality for cancer immunotherapy because of their potent efficacy against terminal cancers. They are known to exert higher efficacy than monoclonal antibodies and antibodydrug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors.KEYWORDS: chimeric antigen receptor, CAR T cells, adoptive cell therapy, ACT, T cell receptor, TCR, cancer, immunotherapy


2021 ◽  
Author(s):  
Zachary L Skidmore ◽  
Hans Rindt ◽  
Shirley Chu ◽  
Bryan Fisk ◽  
Catrina Fronick ◽  
...  

Background: Spontaneous cancers in companion dogs are increasingly recognized as robust models of human disease. This recognition has led to translational clinical trials in companion dogs with osteosarcoma, lymphoma, melanoma, squamous cell carcinoma, and soft tissue sarcoma. The ability to precisely track tumor-specific immune responses in such clinical trials would benefit from reagents to perform species-specific single cell T cell receptor sequencing (scTCRseq). This technology defines clones of T cells reacting to immune interventions and can help identify the specific epitope of response. Single cell gene expression data give insights into the activity and polarization of the T cell. To date, scTCRseq has not been demonstrated for canine samples. Methods: Samples from two responding dogs in a trial of an autologous deglycosylated melanoma vaccine were selected to demonstrate applicability of scTCRseq in a cancer immunotherapy setting. A single-cell suspension of cryopreserved peripheral blood mononuclear cells (PBMC) was prepared for 10X single cell sequencing. Full length 10X cDNA was amplified using a custom-designed nested PCR of the alpha/beta V(D)J region. A library made from this enriched product (scTCRseq) and a 10X gene expression (GEX) library (scRNAseq) were sequenced on the NovaSeq 6000. Results: 1,850-2,172 estimated V(D)J-expressing cells yielded 87-103.7 million reads with 73.8%-75.8% mapped to a V(D)J gene (beta/alpha chains ratio 1.5:1). 43 TRAJ, 29 TRAV, 12 TRBJ, and 22 TRBV gene segments were observed representing 72.9%, 51.8%, 100%, and 62.9% of all known V and J gene segments respectively. A large diversity of clonotypes was captured with 966-1,253 TRA/TRB clonotypes identified. Both dogs also exhibited a small number of highly abundant T cell clonotypes suggesting the presence of an anti-tumor T cell population. GEX enriched libraries successfully defined large clusters of CD8+ and CD4+ T cells that overlapped with V(D)J-expressing cells. Discussion: The developed reagents successfully generated scTCRseq data, for the first time, which allowed the T cell repertoire to be surveyed in dogs responding to anti-tumor immunotherapy. These reagents will allow longitudinal tracking of anti-tumor T cell dynamics in canine cancer immunotherapy trials.


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