{"id":104989,"date":"2021-02-11T16:12:23","date_gmt":"2021-02-11T20:12:23","guid":{"rendered":"http:\/\/www.bu.edu\/eng\/?p=104989"},"modified":"2022-10-28T18:53:40","modified_gmt":"2022-10-28T22:53:40","slug":"wong-lab-develops-smarter-cancer-killing-cells","status":"publish","type":"post","link":"https:\/\/www.bu.edu\/eng\/2021\/02\/11\/wong-lab-develops-smarter-cancer-killing-cells\/","title":{"rendered":"Wong Lab Develops Smarter Cancer-Killing Cells"},"content":{"rendered":"

A system of engineered cells that communicate, targeting autoimmune diseases too<\/h2>\n

By Patrick L. Kennedy<\/strong><\/p>\n

New research out of the College of Engineering could enable doctors to program a patient\u2019s immune system with a more versatile toolkit than ever before in the fight against cancer, as well as autoimmune diseases. Associate Professor Wilson Wong (BME) and colleagues published their study this month in Nature Communications<\/em>.<\/p>\n

Wong\u2019s team approaches the immune system as a computing circuit, which in many ways it resembles. They are reprogramming the circuit to identify and eliminate tumor cells that it\u2019s not catching automatically. Existing immunotherapies do this, but not with the same simultaneous level of specificity and broadness as Wong\u2019s system.<\/p>\n

This latest development in synthetic biology is part of Wong\u2019s ongoing work<\/a> to improve upon chimeric antigen receptor (CAR) T-cell treatments. In conventional CAR-T therapy, T-cells are extracted from a patient\u2019s blood sample and then modified to attack specific antigens (receptor molecules) on the patient\u2019s tumor cells. But the treatment can backfire by triggering a massive release of cell-killing substances called cytokines, which can be life-threatening.<\/p>\n

What Wong\u2019s lab<\/a> has developed in recent years is a CAR-T system that is split<\/em>, universal<\/em>, and programmable<\/em> (SUPRA). That means it can target two types of antigens, making it effective against a wider variety of cancers, and it can be deactivated to prevent cytokine-induced side effects.<\/p>\n

In their new study, Wong\u2019s team further tweaked their CAR-T cells by adding a third target antigen, meaning the engineered immune cells can operate with a higher degree of specificity. To explain the advantages of being more specific, Wong poses the analogy of a detective searching for a crime suspect. If all he has to go on is that the suspect \u201cwears glasses,\u201d that doesn\u2019t narrow the field much. If he learns he\u2019s looking for someone with glasses and <\/em>a beard, he might be getting somewhere. Now, if the suspect has glasses, a beard, and a purple beret, then the detective has a clear idea of what he\u2019s looking for.<\/p>\n

\"\"
A schematic of a CAR circuit that enables T cells to logically detect three antigens.<\/figcaption><\/figure>\n

Wong\u2019s cancer-killing T-cells, similarly, are more effective because they know what characteristics (in their case, antigens) they\u2019re really looking for. They can even be programmed with what the team calls \u201cNOT logic,\u201d ordering them to search for \u201cA and B and not C.\u201d (So glasses and beard, but not <\/em>the purple beret.)<\/p>\n

Moreover, Wong\u2019s team showed that their SUPRA system works not just in T-cells but in multiple immune cell types. That should pave the way for safer therapies for cancer as well as autoimmune disorders such as arthritis and multiple sclerosis. The system can also suppress the immune response that leads to organ transplant rejection.<\/p>\n

It\u2019s worth noting that Wong\u2019s lab accomplished these advances by applying distributed computing principles to the engineered immune cells as a system. \u201cIn computer science, distributed computing is about having multiple computers that all do pieces of the computation, and then they combine to solve the bigger problem\u2014that way, each computer doesn\u2019t need to be a super-computer,\u201d Wong explains. \u201cWe\u2019ve kind of done that by splitting the parts of the computation among different cell types and having them come together to form a program.\u201d<\/p>\n

Finally, the cells are directed to target specific antigens by way of a new synthetic intracellular communication channel that Wong and colleagues have engineered. \u201cEach cell type is tasked with sensing and producing a specific subset of inputs and outputs,\u201d the co-authors write in the paper. \u201cImmune cells can directly communicate with each other to attain temporally choreographed responses.\u201d<\/p>\n

Wong\u2019s collaborators on the study were James J. Collins, the former ENG professor who pioneered synthetic biology; former PhD student Jang Hwan Cho (\u201919); former ENG postdoc Atsushi Okuma; former master\u2019s student Katri Sofjan (\u201919); and PhD student Seunghee Lee. The SUPRA technology is licensed to Senti Bioscience, co-founded by Wong and Collins.<\/p>\n

The full article is available at the Nature Communications <\/em>website.<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

A system of engineered cells that communicate, targeting autoimmune diseases too By Patrick L. Kennedy New research out of the College of Engineering could enable doctors to program a patient\u2019s immune system with a more versatile toolkit than ever before in the fight against cancer, as well as autoimmune diseases. Associate Professor Wilson Wong (BME) […]<\/p>\n","protected":false},"author":2662,"featured_media":127758,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[236,257,899,541,535,255,540],"tags":[618,619,273,302,258,620,621,622,274,623,320,624,625,626,627,628,629,630,631,544,632,633,634],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/104989"}],"collection":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/users\/2662"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/comments?post=104989"}],"version-history":[{"count":6,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/104989\/revisions"}],"predecessor-version":[{"id":127961,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/posts\/104989\/revisions\/127961"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/media\/127758"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/media?parent=104989"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/categories?post=104989"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bu.edu\/eng\/wp-json\/wp\/v2\/tags?post=104989"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}