Cytotoxic T lymphocyte-associated antigen 4 inhibition increases the antitumor activity of adoptive T-cell therapy when carried out with naïve rather than differentiated T cells

Oncology Reports
Takeshi IshikawaToshikazu Yoshikawa

Abstract

Although treatment with an antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) combined with multiple therapeutic interventions has been explored, the effect of combination therapy with CTLA-4 inhibition and adoptive T-cell therapy has not been determined. In the present study, our aim was to determine whether CTLA-4 inhibition, combined with adoptive transfer of T cells at different stages of differentiation, exhibits synergistic antitumor effects in a murine colon cancer model. Mice bearing subcutaneous tumors were administered adoptive T-cell transfer of CD62Lhigh or CD62Llow cells combined with an anti-CTLA-4 antibody (α-CTLA-4) or control immunoglobulin G. Subcutaneous tumors were harvested, and the antitumor effects and helper T-cell polarization were analyzed. CTLA-4 inhibition combined with CD62Lhigh cell administration showed the strongest antitumor effect. Combination therapy increased the number of CD3+ cells within the tumor. Moreover, CTLA-4 inhibition induced polarization of T cells infiltrating the tumor toward the T helper 1 lineage, and suppressed the frequency of regulatory T cells within the tumor, particularly in combination with CD62Lhigh T-cell transfer. This is the first report demonstra...Continue Reading

References

Jun 1, 1996·The Journal of Experimental Medicine·M F Krummel, J P Allison
Aug 1, 1996·The Journal of Experimental Medicine·N J KarandikarJ A Bluestone
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·A A HurwitzJ P Allison
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·E D KwonM B Burg
Jan 25, 2002·European Journal of Immunology·Rebecca J GreenwaldArlene H Sharpe
Mar 22, 2002·Nature Reviews. Immunology·M L AlegreC B Thompson
Mar 27, 2003·Nature Reviews. Immunology·Jeffrey A Bluestone, Abul K Abbas
Jun 17, 2003·Immunology·Arne N AkbarMilica Vukmanovic-Stejic
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·F Stephen HodiGlenn Dranoff
Sep 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Chrysoula I LiakouPadmanee Sharma
Jan 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karsten A PilonesSandra Demaria
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
Jun 7, 2011·The New England Journal of Medicine·Caroline RobertJedd D Wolchok
Jan 9, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antoni RibasAxel Hauschild

❮ Previous
Next ❯

Citations

Aug 25, 2015·BMC Medicine·Sathana DushyanthenSherene Loi

❮ 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.