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[21] [22] In the early 1990s, James Allison showed that CTLA-4 acts as an inhibitory molecule to restrict T-cell responses. In 1996, Allison was the first to show that antibody blockade of a T-cell inhibitory molecule (known as CTLA-4) could lead to enhanced anti-tumor immune responses and tumor rejection.
CTLA-4 is a member of the immunoglobulin superfamily that is expressed by activated T cells and transmits an inhibitory signal to T cells. CTLA-4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and B7-2 respectively, on antigen-presenting cells. CTLA-4 binds CD80 and CD86 with ...
James P. Allison (born 1948) United States "for explaining how CD28 and CTLA-4 are regulators of T cell activation, modulating immune response." University of Texas: Jeffrey Bluestone (born 1954) United States University of California, San Francisco: Craig B. Thompson (born 1953) United States Memorial Sloan Kettering Cancer Center: Gordon J ...
Cancer Therapy by Inhibition of Negative Immune Regulation (CTLA4, PD1) A2AR & A2BR: The Adenosine A2A receptor is regarded as an important checkpoint in cancer therapy because adenosine in the immune microenvironment, leading to the activation of the A2a receptor, is negative immune feedback loop and the tumor microenvironment has relatively high concentrations of adenosine. [27]
Bluestone's lab published studies, one together with Krummel and Allison, for in vitro studies of CTLA-4 function. [78] [79] In collaboration with Mark Jenkins, they were able to see effects of anti-CTLA-4 antibodies in vivo in an immunization setting, [80] but did not effectively carry this into tumor biology. Linsley and colleagues had made ...
James Allison, now at the University of Texas MD Anderson Cancer Center, was an early pioneer of immunotherapy. He discovered that CTLA-4 inhibits T cells from fully attacking, and hypothesized that blocking CTLA-4 could unleash the immune system to fight cancer. Initially, his idea was met with skepticism, but he continued his research and ...
1995 – James P. Allison is the first to describe the function of the critical immune checkpoint CTLA-4; 1995 – Regulatory T cells (Shimon Sakaguchi) 1995 – First Dendritic cell vaccine trial reported by Mukherji et al. 1995 – Discovery of the insect Imd NF-κB pathway [18]
The first checkpoint antibody approved by the FDA was ipilimumab, approved in 2011 for treatment of melanoma. [2] It blocks the immune checkpoint molecule CTLA-4.Clinical trials have also shown some benefits of anti-CTLA-4 therapy on lung cancer or pancreatic cancer, specifically in combination with other drugs.