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Viktor Adalsteinsson

KI alum Viktor Adalsteinsson develops liquid biopsies to detect cancer

Slice of MIT

Cancer patients who undergo surgery are often left with a frightening question: Did the surgeons get all the cancerous cells? No one wants a recurrence of disease, but additional treatments such as radiation or chemotherapy have significant side effects. That’s why Viktor Adalsteinsson PhD ’15 has been developing tools to support better-informed treatment decisions: so-called “liquid biopsies” that can detect the presence of cancer from a simple blood test.

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Curiosity: A Tribute to Steven Keating

MIT Koch Institute

With deep admiration for his ready and profound intellectual curiosity, the Koch Institute notes the passing of Steven Keating SM ’12, PhD ’16, from brain cancer at the age of 31. Then a graduate student in mechanical engineering, Keating spoke about his experience with cancer as part of the Koch Institute’s with/in/sight public lecture series in 2014, shortly after surgery to remove a baseball-sized tumor from his brain.

Like many at MIT, he loved data, and he collected a great deal of his own—everything from scans to sequencing information, including 3D computer analyses he used to fabricate models of his own tumor and pilot a technique for faster, cheaper, and better modeling. In fact, it was the IDH mutation revealed by his tumor biopsy that led Keating to the Koch Institute, where Matthew Vander Heiden and Bridge Project collaborators are using 2HG, an ongogenic metabolite produced by mutant IDH, as a biomarker to detect and monitor IDH-mutant cancers. Citing the role knowledge of his previous MRI scans played in his timely diagnosis, Keating became a passionate advocate for patients to have better access to their own health information and for open-sourcing patient data to advance research on cancer and other diseases. 

The Hitchhiker's Guide to Immunotherapy

MIT News

It's no Ford Prefect, but this is one CAR-T that's going places. New research from KI and Marble Center for Cancer Nanomedicine member Darrell Irvine and fellow immune engineer Dane Wittrup, published in Science, takes advantage of the Irvine Lab's hitchhiking vaccine technology to turbo-charge T cells. By stimulating engineered cells' CARs (chimeric antigen receptors) inside the lymph node, the repurposed vaccine was able to activate and expand the population of tumor-killing T cells for a variety of cancer types, including solid tumors for which immunotherapy has previously proven ineffective. The technology has been licensed to biotechnology company Elicio Therapeutics and is expected to begin clinical tests within the next few years. So long and thanks for all the antigens!

Unmasking Mutant Cancer Cells

Clinical Cancer Research

Researchers in the Jacks and White Laboratories have identified a new dosing routine for a well-studied class of anti-cancer drugs that makes tumor cells more easily recognizable to the immune system. The team found that trading traditional bolus dosing for sustained, low-level dosing of heat shock protein (HSP) inhibitors increased the number of mutated protein fragments presented on the surfaces of tumor cells. Their approach, described in Clinical Cancer Research, could improve immunotherapy's effectiveness across more cancer types with fewer side effects and reinvigorate clinical investigations of promising HSP inhibitors. The research was inspired by and builds on work, partly supported by the Koch Institute Frontier Research Program, of late MIT biologist and KI member Susan Lindquist.

Taris Touts Trial Success

MIT Koch Institute

Taris Biomedical, founded by David H. Koch Professor of Engineering Michael Cima and David H. Koch Institue Professor Robert Langer, has made exciting headway in translating its approach to treating muscle-invasive bladder cancer. TAR-200 is an implantable device developed by the Cima and Langer Labs that continuously administers gemcitabine, a chemotherapy drug, for multiple weeks. First, Taris shared positive results from an ongoing study of the device alone, which suggest therapeutic benefit to both patients who undergo radical cystectomy and those unfit for surgical intervention. Two weeks later, the company announced the dosing of the first patient in a new clinical trial, in collaboration with Bristol-Myers Squibb, that combines the device with nivolumab, an approved cancer immunotherapy.

Killing Tumors with Cytokine-ness

MIT News

Immune cell signaling proteins, known as cytokines, are highly toxic—not just to tumors but, unfortunately, to healthy tissue as well. Wittrup Lab researchers are delivering cytokines directly into solid tumors and using the collagen-binding protein lumican to confine these cell-killing proteins within the tumoral space. Their strategy, described in Science Translational Medicine, leverages the protective layer of collagen produced by the cancer cells to prevent leakage of these toxic agents into the bloodstream and opens up previously-closed avenues for combination immunotherapy. 

Compound Interest

MIT News

Researchers in the laboratories of KI faculty members Michael Hemann and Graham Walker discovered a compound that may make cancer cells more susceptible to cisplatin and similar cancer therapies on the first and, importantly, subsequent doses. Cisplatin and drugs like it work by severely damaging the DNA of cancer cells, which have often lost one of the more reliable means of DNA repair. The newly-identified compound, known as JH-RE-06, interferes with a key component of translesion synthesis, a less accurate DNA repair pathway that not only helps cells survive chemotherapy, but introduces mutations that might confer resistance to future treatment. The study, appearing in Cell and funded in part by the MIT Center for Precision Cancer Medicine, found that the combination killed many more cells than cisplatin alone and that surviving cells were far less able to generate new mutations.

Better Breast Cancer Risk Prediction

MIT Koch Institute

A deep-learning model developed by KI member and Delta Electronics Professor Regina Barzilay can predict from a mammogram if a patient is likely to develop breast cancer within five years. Trained on mammograms and outcomes from more than 60,000 patients at Massachusetts General Hospital, the model learned to spot patterns in mammograms that are precursors to malignant tumors. Published in Radiologythe model performed significantly better than existing approaches, and could be used in the future to build personalized breast cancer screening plans. Read more.

At last month's SOLUTIONS with/in/sight, Barzilay was joined by her co-author, Harvard Medical School Professor and Director of Breast Imaging at Massachussetts General Hospital Constance Lehman, to talk about the new model and earlier work using deep-learning models to screen for dense breast tissue. Managing Director of The Boston Globe and STAT Linda Pizzuti Henry moderated the discussion, with an introduction from MIT president emerita and KI faculty member Susan Hockfield. Watch video

Guiding Light

MIT News

A new system developed by the laboratory of KI member and James Mason Crafts Professor Angela Belcher could pinpoint ovarian tumors during debulking surgery and improve survival rates for patients. Most ovarian cancers are diagnosed in advanced stages of the disease, after tumors—often quite small—have spread so abundantly throughout the abdomen that it is difficult for a surgeon to remove them all. In a mouse study led by Mazumdar-Shaw International Oncology Fellow Neelkanth Bardhan and published in ACS Nano, researchers identified tumors as small as 0.2 millimeters with a combination of near-infrared light and single-walled carbon nanotubule probes. Researchers are seeking approval for a FDA phase 1 clinical trial for the system and plan to adapt it for monitoring patients for recurrence of tumors and for early-stage diagnosis of ovarian cancer. The system was developed with support from the Koch Institute Frontier Research Program and later tested with support from the Bridge Project.

 Aneuploidy in Prostate Cancer

MIT News

Prostate cancers with higher levels of aneuploidy—an abnormal number of chromosomes—also come with higher lethality risk for patients, according to a new study from a Bridge Project team co-led by Angelika Amon, KI member and Kathleen and Curtis Marble Professor in Cancer Research, and Harvard T.H. Chan School of Public Health faculty member Lorelei Mucci. Using a collection of prostate cancer tumor samples, researchers extrapolated the degree of aneuploidy from each sample's genetic sequencing information and compared it to information about patient outcomes. Patients with a higher degree of aneuploidy were five times more likely to die from the disease. The findings, published in Proceedings of the National Academy of Sciencessuggest that aneuploidy could be used to more accurately predict patients' prognosis and to identify patients who might need more aggressive treatment. 

Alpaca Punch

MIT News

In two studies appearing in Proceedings of the National Academy of Sciences, researchers from the laboratory of Richard Hynes, KI member and Daniel K. Ludwig Professor for Cancer Research, showed how tumors and metastases could be imaged and treated with lightweight antibodies (or, "nanobodies") derived from alpacas. The nanobodies target the extracellular matrix (ECM), which plays important roles in cancer cell survival, invasion, and development, and is more genetically stable, less heterogenous, and easier to access than cancer cells.

The researchers, led by Mazumdar-Shaw International Oncology Fellow Noor Jailkhani, built a nanobody library for ECM proteins that were abundant in the tumor microenvironment, but absent from healthy tissues. In one study, researchers treated mouse cancer models with radioisotope-labled nanobodies. PET/CT imaging revealed clearly visible tumors and metastases. In the companion study, they used the same nanobodies to develop nanobody-based chimeric antigen receptor (CAR) T cells to target solid tumors.