Immuno-oncology Research

See how researchers use SBI’s Lentivirus Production and Gene Expression products and services for successful, high-impact immuno-oncology studies.

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How do researchers keep successful immuno-oncology studies on track? With reliable, high-performance, and easy-to-use products and services. See how SBI’s Lentivirus Packaging and Gene Expression Systems products supported a range of high-impact immuno-oncology publications below. And then use the links below to start your order.

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Immuno-oncology Products

Immuno-oncology Services


Select 2018 Immuno-oncology Publications that use SBI Products

Expressing CAR-T Constructs:

 

Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses.
Cho JH, Collins JJ, Wong WW
Cell. 2018 May 31; 173(6):1426-1438.e11. Epub 2018 Apr 26.
PMID: 29706540 PMCID: PMC5984158 [Available on 2019-05-31] DOI: 10.1016/j.cell.2018.03.038

 

What the authors accomplished:

Cho, et al., created an improved CAR-T construct—SUPRA CAR for Split, Universal, and Programmable CAR—that supports re-targeting the CAR without having to reengineer the cell, tunable T-cell activation, the ability to integrate the signal from multiple antigens using logical operators and respond appropriately, and the ability to inducibly control cell type-specific signaling.

 

Quote to Note:

“SUPRA CAR: The Swiss Army Knife of CAR”

 

How SBI helped:

Cho, et al, used a split CAR approach to achieve their goals, expressing the invariable transmembrane base of the CAR (zipCAR) as one amino acid chain and the variable, scFv portion of the CAR (zipFv) as a second amino acid chain that attaches to the zipCAR via a leucine zipper. To express zipCARs in Jurkat cells, Cho, et al., turned to SBI’s piggyBac expression system. With piggyBac, you get easy, consistent transgenesis that enables integration of DNA of up to 100 kb in length, and the option to remove the inverted terminal repeats (ITRs) and piggyBac sequences leaving only the DNA cargo integrated into the genome.

Sorting tumor cells in an orthotopic mouse model of breast cancer:

 

A tumor-myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer.
Kuan EL, Ziegler SF. Nat Immunol. 2018 Apr; 19(4):366-374.
PMID: 29556001 PMCID: PMC5864553 DOI: 10.1038/s41590-018-0066-6

 

What the authors accomplished:

Kuan and Ziegler expanded our knowledge on how tumor cells manipulate the immune response into promoting tumor cell growth through a previously unknown tumor-myeloid cell signaling pathway. Through the use of both orthotopic and autochthonous mouse models of metastatic breast cancer, the authors showed that secretion of IL-1α by tumor cells induced infiltrating myeloid cells to secrete the cytokine TSLP (thymic stromal lymphopoietin) and that TSLP, normally involved in promoting T helper type 2 (TH2) cell responses, in turn promotes tumor cell survival by activating the anti-apoptosis protein Bcl2 and driving metastasis.

 

Quote to Note:

“These data suggest that the role of TSLP in tumorigenesis can be complex and is determined by the specific TSLP-responding cell type(s) involved and its (their) importance in regulating tumor development.”

 

How SBI helped:

To create their orthotopic mouse breast tumor model, Kuan and Ziegler injected 4T1 mammary carcinoma cells into mouse mammary glands. In some of their studies, they used 4T1 cells that had been transduced with SBI’s pCDH-CMV-MCS-EF1α-GreenPuro Cloning and Expression Lentivector (Cat# CD513B-1). This construct delivers strong GFP expression, which enabled the authors to use flow cytometry to sort 4T1-GFP tumor cells (CD45- EpCAM+GFP+) from the day 28 primary tumor in 4T1-GFP tumor-bearing mice.

Getting consistently robust transgene expression for immunotherapy development:

 

“SBI’s custom cloning and virus packaging services have been invaluable in moving our multiple time-sensitive projects in the right direction and, with their expertise in vector design, we have been able to successfully infect and express our transgenes at levels that have exceeded our expectations!”

—Dr. Gurpanna Saggu, Cue Biopharma™, MA

Cue Biopharma is an immunotherapy company developing biologics engineered to selectively modulate disease-relevant T cells for the treatment of cancer.

Supporting si/shRNA knockdown creation and luciferase reporter expression in ECs and macrophages:

Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α.
Wang Q, et al. Nat Commun. 2018 Feb 8; 9(1):559.
PMID: 29422647 PMCID: PMC5805734 DOI: 10.1038/s41467-018-03050-0

 

What the authors accomplished:

Wang, et al., were able to characterize a previously unknown mechanism for tumor-promoting alternative macrophage activation in glioblastoma (GBM). Starting with the identification of markers for alternatively-activated macrophages and the observation that these cells cluster near CD31+ vascular endothelial cells (ECs), the authors used reporter assays and si/shRNA knockdowns to show that ECs in a GBM microenvironment secrete IL-6 and CSF-1, which together promote alternative macrophage activation via Akt/mTOR/PPARγ transcriptional activation of HIF-2α. They also demonstrated the critical role that IL-6 plays in alternative activation by showing that EC-specific conditional IL-6 knockout mice increased survival and showed decreased tumor volume.

 

Quote to Note:

“Thus, targeting IL-6 may offer exciting therapeutic opportunities to reactivate macrophage-mediated tumor immunity, which may block tumor progression and treatment resistance.”

 

How SBI helped:

A luciferase reporter and si/shRNA knockdowns of specific transcripts were critical for Wang, et al.’s, demonstration of the role of IL-6, CSF-1, HIF-2α, and PPARγ in alternative macrophage activation in GBM. SBI’s consistent and reliable pPACKH1 Lentivirus Packaging System were used to deliver all of these constructs into either EC cells or bone marrow derived macrophages (BMDM). In addition, the luciferase reporter used in this study was expressed using an SBI pCDH Lentivirus Expression Vectors which deliver robust expression in a range of cell types.