for their discovery of cancer therapy by inhibition of negative immune regulation
SUMMARY
Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy.
James P. Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors. He then developed this concept into a brand new approach for treating patients.
In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a different mechanism of action. Therapies based on his discovery proved to be strikingly effective in the fight against cancer.
Allison and Honjo showed how different strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. The seminal discoveries by the two Laureates constitute a landmark in our fight against cancer. 0008マンセー生物学2018/10/01(月) 20:16:58.87ID:6H+jkviO Key publications
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992). Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 11(11), 3887–3895.
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996). Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271(5256), 1734–1736.
Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C., Feldhaus, A. L., Greenberg, N. M., Burg, M.B. & Allison, J.P. (1997). Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci USA, 94(15), 8099–8103.
Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999). Development of Lupus-like Autoimmune Diseases by Disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 11, 141–151.
Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., Horton, H.F., Fouser, L., Carter, L., Ling, V., Bowman, M.R., Carreno, B.M., Collins, M., Wood, C.R. & Honjo, T. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med, 192(7), 1027–1034. 0009マンセー生物学2018/10/01(月) 20:20:30.82ID:6H+jkviO Hodi, F.S., Mihm, M.C., Soiffer, R.J., Haluska, F.G., Butler, M., Seiden, M.V., Davis, T., Henry-Spires, R., MacRae, S., Willman, A., Padera, R., Jaklitsch, M.T., Shankar, S., Chen, T.C., Korman, A., Allison, J.P. & Dranoff, G. (2003). Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA, 100(8), 4712-4717.
The Royal Swedish Academy of Scienceshas decided to award the Nobel Prize in Physics 2018
“for groundbreaking inventions in the field of laser physics”
with one half to
Arthur Ashkin
Bell Laboratories, Holmdel, USA “for the optical tweezers and their application to biological systems”
and the other half jointly to
Gérard Mourou École Polytechnique, Palaiseau, France University of Michigan, Ann Arbor, USA
and
Donna Strickland University of Waterloo, Canada
“for their method of generating high-intensity, ultra-short optical pulses” 0019マンセー生物学2018/10/03(水) 15:12:41.58ID:mZtF9L7s Tools made of light
The inventions being honoured this year have revolutionised laser physics. Extremely small objects and incredibly rapid processes are now being seen in a new light. Advanced precision instruments are opening up unexplored areas of research and a multitude of industrial and medical applications.
Arthur Ashkin invented optical tweezers that grab particles, atoms, viruses and other living cells with their laser beam fingers. This new tool allowed Ashkin to realise an old dream of science fiction – using the radiation pressure of light to move physical objects. He succeeded in getting laser light to push small particles towards the centre of the beam and to hold them there. Optical tweezers had been invented.
A major breakthrough came in 1987, when Ashkin used the tweezers to capture living bacteria without harming them. He immediately began studying biological systems and optical tweezers are now widely used to investigate the machinery of life. 0020マンセー生物学2018/10/03(水) 15:14:51.67ID:mZtF9L7s Gérard Mourou and Donna Strickland paved the way towards the shortest and most intense laser pulses ever created by mankind. Their revolutionary article was published in 1985 and was the foundation of Strickland’s doctoral thesis.
Using an ingenious approach, they succeeded in creating ultrashort high-intensity laser pulses without destroying the amplifying material. First they stretched the laser pulses in time to reduce their peak power, then amplified them, and finally compressed them. If a pulse is compressed in time and becomes shorter, then more light is packed together in the same tiny space – the intensity of the pulse increases dramatically.
Strickland and Mourou’s newly invented technique, called chirped pulse amplification, CPA, soon became standard for subsequent high-intensity lasers. Its uses include the millions of corrective eye surgeries that are conducted every year using the sharpest of laser beams.
The innumerable areas of application have not yet been completely explored. However, even now these celebrated inventions allow us to rummage around in the microworld in the best spirit of Alfred Nobel – for the greatest benefit to humankind. 0021マンセー生物学2018/10/03(水) 15:22:14.16ID:mZtF9L7s 賞金1/2, 1/4, 1/4で分配らしい 0022マンセー名無しさん2018/10/03(水) 18:36:19.11ID:wHPoNniD 「いつか遺伝子をピンセットで手術するように云々」って文章に感動したのが臨床から研究に転換したって記事が新聞に載ってたけど 発達障害で苦しむねらー諸君の心にも響きそうやね いやむしろそれくらい当然だろう早くしろと言い出すのか 何にしろ苦しむ奴が居なくなれば良いけどもそれも生物学と優生学の問題がまた出てくるんやろうね 0023マンセー名無しさん2018/10/03(水) 18:46:27.00ID:mZtF9L7s>>22 発達障害は遺伝子によるものやないやろ エピジェネティクスなら関係あるかもしれんけど 先ずは致死性の遺伝子疾患の治療に使われるやろな 倫理的な問題は出てくるけど医学の原則から外れるものやないやろ 去勢のようなものやないんやから 遺伝子を変えてはならん決まりはあらへん 0024マンセー名無しさん2018/10/03(水) 18:55:45.11ID:wHPoNniD そのタイプの関係の仕方ならあらゆる病気にも言えるんやない 自閉症なんかだと遺伝子のコピーミスが原因って聞いたけど
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2018
with one half to
Frances H. Arnold California Institute of Technology, Pasadena, USA
“for the directed evolution of enzymes”
and the other half jointly to
George P. Smith University of Missouri, Columbia, USA
and
Sir Gregory P. Winter MRC Laboratory of Molecular Biology, Cambridge, UK
“for the phage display of peptides and antibodies” 0033マンセー名無しさん2018/10/07(日) 09:49:20.81ID:DqtCJAim They harnessed the power of evolution The power of evolution is revealed through the diversity of life. The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and in some cases cure metastatic cancer.
Since the first seeds of life arose around 3.7 billion years ago, almost every crevice on Earth has filled with different organisms. Life has spread to hot springs, deep oceans and dry deserts, all because evolution has solved a number of chemical problems. Life’s chemical tools – proteins – have been optimised, changed and renewed, creating incredible diversity.
This year’s Nobel Laureates in Chemistry have been inspired by the power of evolution and used the same principles – genetic change and selection – to develop proteins that solve mankind’s chemical problems. 0034マンセー名無しさん2018/10/07(日) 09:53:38.69ID:DqtCJAim One half of this year’s Nobel Prize in Chemistry is awarded to Frances H. Arnold. In 1993, she conducted the first directed evolution of enzymes, which are proteins that catalyse chemical reactions. Since then, she has refined the methods that are now routinely used to develop new catalysts. The uses of Frances Arnold’s enzymes include more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels for a greener transport sector.
The other half of this year’s Nobel Prize in Chemistry is shared by George P. Smith and Sir Gregory P. Winter. In 1985, George Smith developed an elegant method known as phage display, where a bacteriophage – a virus that infects bacteria – can be used to evolve new proteins. Gregory Winter used phage display for the directed evolution of antibodies, with the aim of producing new pharmaceuticals. The first one based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Since then, phage display has produced anti-bodies that can neutralise toxins, counteract autoimmune diseases and cure metastatic cancer.
We are in the early days of directed evolution’s revolution which, in many different ways, is bringing and will bring the greatest benefit to humankind. 0035マンセー名無しさん2018/10/07(日) 10:21:01.68ID:DqtCJAim 化学賞は女性が賞金1/2か 今年の自然科学のノーベル賞は全て生物学と関係が深い分野であり生物学がホットであることが改めて感じられる 0036マンセー名無しさん2018/10/07(日) 19:30:37.22ID:DQN6NzrB まあ我々凡俗には関係無いけどな 0037マンセー名無しさん2018/10/07(日) 19:38:49.20ID:DqtCJAim>>36 卑下するな 医療に応用されて一般庶民にも還元される技術や 享受しよや 0038マンセー名無しさん2018/10/07(日) 20:15:45.56ID:DQN6NzrB iPS細胞だったかが発見から実用化までにざっと40年はかかるんやろ 確かに物理学を応用したレーザーピンセットやら進化論を応用した酵素の創出なんてのは凄いわ オプシーボも癌になった場合に使うかもしれん身近な分野や やけどオプシーボは全体の4割、それも重篤な癌患者の中の4割しか効かんのやろ?しかも莫大な金がかかる 現代の日本の社会保障の増加まで考えればワイらがこれらの技術を実際に応用したものを使うって事は考えにくいやろ 生物学がホットやと喜ぶのもええけど生物学系の大卒でも無けりゃほぼ関係ないんちゃうか
The Nobel Assembly at Karolinska Institutet has today decided to award the 2019 Nobel Prize in Physiology or Medicine jointly to William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza for their discoveries of how cells sense and adapt to oxygen availability
SUMMARY Animals need oxygen for the conversion of food into useful energy. The fundamental importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown. William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza discovered how cells can sense and adapt to changing oxygen availability. They identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen.
The seminal discoveries by this year’s Nobel Laureates revealed the mechanism for one of life’s most essential adaptive processes. They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function. Their discoveries have also paved the way for promising new strategies to fight anemia, cancer and many other diseases. 0283マンセー名無しさん2019/10/15(火) 23:09:46.02ID:iXzYpn4A Oxygen at center stage Oxygen, with the formula O2, makes up about one fifth of Earth’s atmosphere. Oxygen is essential for animal life: it is used by the mitochondria present in virtually all animal cells in order to convert food into useful energy. Otto Warburg, the recipient of the 1931 Nobel Prize in Physiology or Medicine, revealed that this conversion is an enzymatic process.
During evolution, mechanisms developed to ensure a sufficient supply of oxygen to tissues and cells. The carotid body, adjacent to large blood vessels on both sides of the neck, contains specialized cells that sense the blood’s oxygen levels. The 1938 Nobel Prize in Physiology or Medicine to Corneille Heymans awarded discoveries showing how blood oxygen sensing via the carotid body controls our respiratory rate by communicating directly with the brain. 0284マンセー名無しさん2019/10/15(火) 23:12:00.51ID:iXzYpn4A HIF enters the scene In addition to the carotid body-controlled rapid adaptation to low oxygen levels (hypoxia), there are other fundamental physiological adaptations. A key physiological response to hypoxia is the rise in levels of the hormone erythropoietin (EPO), which leads to increased production of red blood cells (erythropoiesis). The importance of hormonal control of erythropoiesis was already known at the beginning of the 20th century, but how this process was itself controlled by O2 remained a mystery.
Gregg Semenza studied the EPO gene and how it is regulated by varying oxygen levels. By using gene-modified mice, specific DNA segments located next to the EPO gene were shown to mediate the response to hypoxia. Sir Peter Ratcliffe also studied O2-dependent regulation of the EPO gene, and both research groups found that the oxygen sensing mechanism was present in virtually all tissues, not only in the kidney cells where EPO is normally produced. These were important findings showing that the mechanism was general and functional in many different cell types.