A new Cell paper from the Jacks Lab shows how lung cancer can co-opt crosstalk between the lung’s microbiome, or resident bacteria, and the immune system. Generally, resident bacteria in the lung are stable and in relatively low abundance, but in cancer, the system is disrupted. The overall population of bacteria increases, but the diversity of types of bacteria is reduced. Immune cells called gamma delta T cells proliferate and produce cytokines, or signaling molecules, ultimately promoting inflammation and tumor growth and survival. As lung bacteria become more disrupted the cycle intensifies, creating a feedback loop that supports tumor development and progression. Findings from this study have important therapeutic implications, both for breaking the feedback loop via drugs targeting key cytokines or bacterial strains and for intercepting lung cancer by managing the lung bacteria in early-stage or high-risk populations. Read more.

Many congratulations to KI member Angelika Amon on winning a 2019 Vilcek Foundation Prize in Biomedical Science. The prize honors immigrant scientists whose contributions have “extraordinary implications for our understanding of human biology and our prospects for treating human disease.” Amon's work has provided crucial insights into cell growth and division, and how errors in these processes contribute to birth defects and cancer. She and her fellow prizewinners will be honored at a gala in New York this spring. Read more.

Thanks to a fortuitous connection in the Koch Café, it is now possible to longitudinally study cancer progression and treatment response in genetically engineered mouse models using circulating tumor cells. A new microfluidic platform, described in Proceedings of the National Academy of Sciences, combines expertise from the Manalis, Jacks, Shalek, and Vander Heiden Lab to capture and genomically profile these vanishingly rare cells from a single awake mouse without depleting the animal’s limited blood supply. Read more.

In an essay for Science Signaling, KI faculty member Michael Yaffe, the David H. Koch Professor of Science, makes a case for looking at cancer not as a disease of genetics, but as a disease of signaling. Yaffe argues that although genetic approaches have resulted in extraordinary insights into the disease, signaling information should be incorporated into the clinical decision-making process. He advocates for improving protein-based measurement technologies to analyze tumor cell signaling in clinical samples. This emphasis on expanding the cancer research focus from genetics to a broader program is echoed by other researchers and initiatives at MIT. For example, at MIT’s Center for Precision Cancer Medicine (which Yaffe directs), researchers explicitly incorporated non-genomic approaches into the fundamental mission and research portfolio.

A truly inspired combination of messenger RNA with a degradable polymer from the KI’s Anderson and Langer labs may make inhalable mRNA treatments for lung diseases possible. Once inside a cell, mRNA can induce cells to produce disease-fighting proteins, but its therapeutic potential is limited by how quickly and easily the body can break it down. In a proof-of-concept study appearing in Advanced Materials, researchers successfully delivered the combination of mRNA and stabilizing polymer to lung cells in mice using an inhalable mist. The work was partially supported by TranslateBio, which has begun testing an inhalable form of mRNA in a Phase 1/2 clinical trial in patients with cystic fibrosis. Listen in at Scientific American or read more at MIT News.

The Atlantic outlines scientists’ growing realization that the widespread use of generic cell culture media for cancer research may have inadvertently skewed outcomes of animal cell studies for decades. In its examination of the recent push to create media that better reflect the chemical profiles of the cellular environment, the piece highlights KI member David Sabatini’s 2017 study that showed cancer cells are much less responsive to the chemotherapy drug Adrucil when grown in a medium that more closely replicates the nutrients in human blood. Former KI postdoc Alexander Muir also gets a nod for recent work that points to limitations even in these new, more realistic media. The study, which was carried out in the laboratory of KI associate director and MIT Center for Precision Cancer Medicine member Matthew Vander Heiden, shows that nutrient levels of the fluid inside a tumor differ from those in the blood. Read more.

Bioengineering & Translational Medicine published a tribute issue (a.k.a. “festschrift”) in honor of the KI's own Bob Langer and fellow chemical engineering luminary Nicholas Peppas on behalf of the American Institute of Chemical Engineers and its Society for Biological Engineering. In the issue’s foreward, KI alumnus Aaron C. Anselmo writes that their work has “advanced the visibility of drug delivery and biomaterials in the scientific landscape, especially within chemical engineering, and has inspired young professionals to follow their paths.” Read more.

Tyler Jacks sat down with Transnetyx founder and CEO Bob Bean to share his path to cancer research and his insights into building a career in science, the power of mentorship, and putting together a great lab. Listen in at the Highly Cited podcast.

In a review, Bob Langer discussed recent advances, current challenges, and future outlook for harnessing advanced biomaterials and drug delivery systems, such as nanoparticles and engineered T cells, to improve the effectiveness of immunotherapy while reducing toxic side effects. (Nature Reviews Drug Discovery)

The Regev Lab studied the effector response of CD8+ tumor-infiltrating lymphocytes after checkpoint blockade therapy, finding that post-blockade cells could be divided into subsets resembling naive, effector, and memory-precursor cell and that the expression of Tcf7/Tcf1 is required for memory-precursor-like cells and efficacy of immunotherapies. (Immunity)

The Spranger Lab found that tumor-intrinsic WNT/β-catenin signaling is enriched in the non-T cell-inflamed tumor microenvironment, suggesting that pharmacologic inhibitors of the pathway may help restore immune cell infiltration and boost immunotherapy. (Clinical Cancer Research)

Studying the activities of kinase networks in HER2-positive breast cancer cells in response to HER2-targeted drugs, the White Lab identified critical proteins, such as the kinase FAK1, that enabled sustained cell survival. Combining an FAK1 inhibitor with a HER2-blocking agent substantially increased cell death. (Science Signaling)

Trovagene announced a new patent for the use of the drug onvansertib in combination with other anti-androgen drugs for the treatment of prostate cancer. Last fall, Trovagene secured exclusive rights to develop combination therapies and clinical biomarkers for prostate cancer based in part on Bridge Project-funded research. Read more.

Lyndra Therapeutics, co-founded by KI member Bob Langer, raised $55 million in its Series B round, with new investors including the Bill and Melinda Gates Foundation and Gilead Sciences. Phase 2 trials for its ultra long-acting drug delivery capsule are expected to begin next year. Read more.

Dragonfly Therapeutics, co-founded by KI director Tyler Jacks, has committed $10 million to launch the first clinical studies of its TriNKETs (Tri-specific, NK cell Engager Therapies) platform for both solid tumor and hematological cancers. Read more.

Following its record-breaking IPO, Moderna Therapeutics (co-founded by KI member Bob Langer) published preclinical data in Science Translational Medicine demonstrating the promise of its mRNA-2752 program in several cancers. Read more.

Dewpoint Therapeutics launched with a $60 million Series A, aims to translate recent insights into biomolecular condensates from the laboratory of co-founder and KI member Rick Young to drug discovery. Read more.

KI member Bob Langer and collaborator Omid Farokhzad co-founded Seer— combining nanotechnology, protein chemistry, and machine learning—to develop liquid biopsy tests for the early detection of cancer and other diseases. Read more.

Epizyme, co-founded by KI member Bob Horvitz, is submitting a New Drug Application to gain accelerated approval of tazemetostat for patients with relapsed or refractory follicular lymphoma. Read more.

Ribon Therapeutics, founded by former KI member Paul Chang, launched with $65 million in a Series B funding round with Victoria Richon, a veteran of Sanofi and Epizyme, at the helm. Ribon focuses on developing PARP7 inhibitors for cancer treatment. Read more.