CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1

Cancer Immunology, Immunotherapy : CII
Takuya OsadaH Kim Lyerly

Abstract

Bispecific T cell-engaging (BiTE) antibodies recruit polyclonal cytotoxic T cells (CTL) to tumors. One such antibody is carcinoembryonic antigen (CEA) BiTE that mediates T cell/tumor interaction by simultaneously binding CD3 expressed by T cells and CEA expressed by tumor cells. A widely operative mechanism for mitigating cytotoxic T cell-mediated killing is the interaction of tumor-expressed PD-L1 with T cell-expressed PD-1, which may be partly reversed by PD-1/PD-L1 blockade. We hypothesized that PD-1/PD-L1 blockade during BiTE-mediated T cell killing would enhance CTL function. Here, we determined the effects of PD-1 and PD-L1 blockade during initial T cell-mediated killing of CEA-expressing human tumor cell lines in vitro, as well as subsequent T cell-mediated killing by T lymphocytes that had participated in tumor cell killing. We observed a rapid upregulation of PD-1 expression and diminished cytolytic function of T cells after they had engaged in CEA BiTE-mediated killing of tumors. T cell cytolytic activity in vitro could be maximized by administration of anti-PD-1 or anti-PD-L1 antibodies alone or in combination if applied prior to a round of T cell killing, but T cell inhibition could not be fully reversed by this blo...Continue Reading

References

Oct 5, 2001·Nature Genetics·R DerynckA Balmain
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshiko IwaiNagahiro Minato
Oct 31, 2002·Nature Immunology·Hung T Khong, Nicholas P Restifo
Apr 15, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S MosolitsH Mellstedt
Dec 24, 2005·The New England Journal of Medicine·Franck PagèsJérôme Galon
Feb 17, 2007·Nature Immunology·Arlene H SharpeGordon J Freeman
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takeo NomiYoshiyuki Nakajima
Apr 17, 2007·Current Opinion in Immunology·Mary E KeirArlene H Sharpe
Nov 21, 2007·Surgical Oncology Clinics of North America·Soldano Ferrone, Theresa L Whiteside
Mar 12, 2008·The Journal of Experimental Medicine·Sang-Jun HaRafi Ahmed
Apr 17, 2008·Cancer Research·Srinivas Nagaraj, Dmitry I Gabrilovich
Jun 11, 2009·Cancer Research·Patrick A Baeuerle, Carsten Reinhardt
Feb 2, 2010·Annals of Surgical Oncology·Mona KarlssonOla Winqvist
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael A CurranJames P Allison
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jul 1, 2010·International Immunology·Marguerite GhiottoDaniel Olive
Sep 8, 2010·The Journal of Experimental Medicine·Kaori SakuishiAna C Anderson
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jun 5, 2012·The New England Journal of Medicine·Antoni Ribas
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Jun 5, 2012·The New England Journal of Medicine·Julie R BrahmerJon M Wigginton
Oct 17, 2012·Immunology and Cell Biology·Mélissa MathieuNathalie Labrecque

❮ Previous
Next ❯

Citations

Feb 2, 2016·Cancer Biology & Therapy·Bin DongZhong Wang
Oct 21, 2015·Vaccine·Michael A Morse, H Kim Lyerly
Apr 12, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·An LiuZai-Qun Liu
Oct 18, 2016·Trends in Pharmacological Sciences·B Vijayalakshmi AyyarRichard O'Kennedy
Mar 23, 2019·Thoracic Cancer·Yang BaiXing Su
Dec 2, 2017·Nature Reviews. Drug Discovery·Paul J Carter, Greg A Lazar
Jun 9, 2019·Nature Reviews. Drug Discovery·Aran F LabrijnPaul W H I Parren
Jun 30, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aeryon KimXin Yu
Sep 17, 2020·Cancer Biotherapy & Radiopharmaceuticals·Nuthan V BathulaJerrard M Hayes
Jun 8, 2017·Gastroenterology Research and Practice·Joo Han Lee, Seong-Wook Lee
Sep 21, 2018·American Society of Clinical Oncology Educational Book·Michael J OvermanMichael A Morse
Sep 22, 2017·Journal of Hematology & Oncology·Shengnan YuKongming Wu
Apr 22, 2020·Cellular & Molecular Immunology·Heliang LiErwei Song
Jul 16, 2020·Cancers·Eline JanssenDaniele V F Tauriello
Feb 25, 2020·BioMed Research International·Malek KreidiehAli Shamseddine
Jul 16, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuan ChenEmma C Morris
Jul 8, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stijn J H WaaijerMarjolijn N Lub-de Hooge
Jun 20, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Susanne HippPaul J Adam
Jan 21, 2021·Cancers·Jim MiddelburgThorbald van Hall
Feb 18, 2021·Journal of Surgical Oncology·Melissa A Lumish, Andrea Cercek
Aug 24, 2017·Pharmacology & Therapeutics·Z Wu, N V Cheung
Jun 3, 2021·International Journal of Molecular Sciences·Ames C RegisterHo Young Lee
Jun 14, 2021·Cancer Treatment Reviews·Sun Min LimByoung Chul Cho
May 29, 2021·Molecular Cancer Therapeutics·Alison Crawford, Danica Chiu
Jun 11, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Belén BlancoLuis Alvarez-Vallina
Sep 5, 2021·International Journal of Cancer. Journal International Du Cancer·Kevin T LynchCharles M Friel

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.