Nordic Biosite highlights PD-1 Inhibitor role in enhancing cancer immune response


Nordic Biosite highlights PD-1 Inhibitor role in enhancing cancer immune response


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Press Release | Nordic Biosite AB

MARCH 29, 2016

Täby, Sweden: – Nordic BioSite, the leading Scandinavian supplier of validated biotechnology products, has highlighted evidence that Programmed Cell Death Protein 1 (PD-1) is implicated in immune regulatory responses, acting as a negative regulator of T cell activation.

A Nordic BioSite newsletter article ‘PD-1 and PD-L1 Inhibitors in Practice’ suggests that these new insights open up new possible treatment pathways in oncology.

“PD-1 is expressed by activated T cells and there is multiple evidence to suggest that PD-1 is implicated in immune regulatory responses, where it acts as a negative regulator of T cell activation,” says Nordic BioSite.

Reduced T Cells

It points out that separate pieces of research (Nishimura et al. 1999 and 2001) had pointed to lupus-like glomerulonephritis and dilated cardiomyopathy on C57BL/6 and BALB/c backgrounds, respectively being developed in mice with PD-1 knocked out. A further study (Freeman et al., 2000) has found that in vitro, treatment of anti-CD3 stimulated T cells with PD-L1-Ig resulted in reduced T cell proliferation and IFN-γ secretion.

“Upon meeting a target cell expressing a TCR activator, the T cell will get activated and recognize the target cell as hostile. However, in many cancers the PD-1L expression is up-regulated on the target cells and the PD-1:PD-L1/2 interaction inhibits T cell activity and allows cancer cells to escape immune surveillance,” the article states.

Immune checkpoints

PD-1 functions similarly to CTLA-4 as immune checkpoints that are becoming increasingly important in therapeutic development for cancer treatments.

“Using target-specific antibodies against these immune checkpoint markers, the binding between PD-1 and its ligand is obstructed, thereby allowing the T cell to become re-activated and attack the tumor cell. This set-up allows for a tailor-made and more effective regimen with fewer side-effects than traditional chemotherapy treatments,” says Nordic BioSite.

It points out that various clinical trials have been conducted for anti-PD-1/PDL1 in various cancers including, lung adenocarcinom, renal cell carcinoma and bladder cancer. A study published last year by Jennifer Kleponis and others had found that between 10 and 50 per cent of cancer patients with certain types of solid tumors had shown responses to these treatments, leaving room for further development in this research area.

New treatment pathways

“This has prompted researchers to investigate other possible treatment pathways. It is not only the activation of T cells that is of great importance in the fight against tumor cells. In the studies where treatment with immune checkpoint inhibitors was successful, an effector T cell infiltration was a common signature. Thus, even if the PD-1:PD-L1 interaction is blocked, an effective T cell infiltration into the tumor seems to be of great importance for a successful treatment,” says Nordic BioSite.

Cancer vaccines shown to augment effector T cell infiltration seem to be the most promising method to get T cells into the tumors, delivering antigenic epitopes from whole cells into the patient. These antigens are picked up by the patient’s APCs and presented to the effector T cells. In a study on pancreatic cancer, following vaccination the formation of immunotherapy-induced lymphoid aggregates was found within the tumors, suggesting an infiltration of organized and functional immune structures (Lutz et al., 2014).

“Therefore, a combinational treatment including both relevant cancer vaccine and immune checkpoint inhibitors can have a synergic effect in eliciting antitumor immune responses,” the article concludes.

Nordic BioSite’s product portfolio includes blocking antibodies, proteins and flow cytometry antibodies product derived from PD-1, PD-L1 and PD-L2 as well as immunohistochemistry and WB Antibodies for PD-1 and PD-L1.

References:

Nishimura H, Nose M, Hiai H, Minato N, Honjo T (Aug 1999). “Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor”. Immunity 11 (2): 141–51. doi:10.1016/S1074-7613(00)80089-8.

Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo T (Jan 2001). “Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice”. Science 291 (5502): 319–22. doi:10.1126/science.291.5502.319.

Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (Oct 2000). “Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation”. The Journal of Experimental Medicine 192 (7): 1027–34. doi:10.1084/jem.192.7.

Jennifer Kleponis, Richard Skelton, and Lei Zheng (Sep 2015). ”Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors”. Cancer Biol Med.; 12(3): 201–208. doi: 10.7497/j.issn.2095-3941.2015.0046.

Lutz ER, Kinkead H, Jaffee EM, Zheng L. “Priming the pancreatic cancer tumor microenvironment for checkpoint-inhibitor immunotherapy”. Oncoimmunology 2014;3:e962401.

About Nordic BioSite

Since the late 1990s, Nordic BioSite has become recognized as one of the pharma industry’s most innovative and customer-responsive supplier of high quality validated biotechnology products for research, diagnostics, immunology and molecular biology.

The company serves pharmaceutical, biotech, diagnostic and academic organizations with tens of thousands of different products in more than 30 different groups, ranging from antibodies to genetic vectors. These are sourced from selected manufacturers and laboratories in Europe, the Americas and Asia.

Nordic BioSite continuously introduces new products as a result of its own R&D, leveraged by close partnerships with manufacturers and feedback from customers.

Nordic BioSite’s company strapline, By Your Side™, defines a company ethos of partnering life science customers, helping to find the right products and services to help reach chosen goals across the whole spectrum of biotech research areas.

Nordic BioSite also operates as a CRO through its Finnish-based cGLP laboratory, BioSiteHisto. This offers a wide range of leading-edge research-based custom laboratory services including histology, immunochemistry, in vitro research and testing, antibody optimization, antibody conjugation and predesigned adenylated linkers for Next Generation sequencing.

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Nordic BioSite AB
Tel: +46 (0)8 544 433 40
Email: info@nordicbiosite.com

Resources

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Two ways of blocking the interaction between PD-1 and PD-L1, using antibodies and thereby aiding the T cell to get activated and clear target cells

Two ways of blocking the interaction between PD-1 and PD-L1, using antibodies and thereby aiding the T cell to get activated and clear target cells


Supplier Information

Supplier: Nordic Biosite
Address: Propellervägen 4A, 183 62 Täby, Sweden
Tel: +46 (0)8 544 433 40
Fax: +46 (0)8 756 94 90
Website: www.nordicbiosite.com


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