Collaborating against cancer: MIT’s Koch Institute for Integrative Cancer Research

“Culture trumps strategy”. This was the message Institute Professor Philip Sharp delivered at a recent Koch Institute (KI) event. The declaration embodies a philosophy that how we work together is more decisive in achieving superordinate goals than our particular tactics or approaches. At the KI, the culture of cross-disciplinary collaboration is arguably one of its greatest assets in making progress against cancer. The core mission of the institute is to generate new insights, tools, and technologies to better treat, diagnose, and prevent cancer. By bringing together biologists, engineers (chemical, mechanical, biological, and materials science), chemists, computer scientists, and clinicians, the KI catalyzes interdisciplinary approaches in the fight against the disease. Central to the institute’s ability to foster these collaborations is the state-of-the-art cancer research facility on the MIT campus (Figure 1). Since 2010, the KI building has enabled collaborations between the constituent research groups through the physical colocalization of both faculty members from multiple departments and the facilities necessary for advancing cancer research. The KI houses 13 core facilities that provide essential resources and technical support for the cancer research community. These facilities include animal imaging/preclinical testing, bioinformatics, proteomics, transgenics, flow cytometry, genomics, microscopy, histology, nanotechnology, and a zebrafish facility. The end result is that the KI serves as a nucleus for cancer research activities on the MIT campus, and the number of collaborative peer-reviewed publications has doubled since the completion of the building (Figure 2).

Figure 1:

Colocalization. The Koch Institute for Integrative Cancer Research puts biologists, engineers, chemists, computer scientists, and clinicians under one roof. Picture provided courtesy of the Koch Institute.

Figure 2:

Collaborative impact. The number of collaborative publications produced by the institute have doubled since investigators began cohabitating in the new KI building. Data provided courtesy of the Koch Institute.

A mere sampling of this collaborative research in the last year bears witness to the exciting new approaches and discoveries being made. Progress against the disease is being made on multiple fronts: from increasing our fundamental understanding of cancer behavior, generating better models of the disease, improving therapeutic effects, and developing new technology platforms for treatment and detection. To develop better cancer models, researchers in the Jacks, Sharp, and Anderson laboratories applied a new genome-editing technology called CRISPR as a new way of generating mouse models of liver cancer in adult mice [1]. This new approach bypasses the need for embryonic stem cell engineering or extensive breeding of mutant strains that are often time-consuming, and it can facilitate the evaluation of the oncogenic potential of candidate cancer genes, either individually or in combination with other cancer genes. To facilitate tumor cell detection and visualization, the Belcher and Bhatia laboratories developed tumor-targeted carbon nanotubes [2]. This new platform enabled real-time visualization of tumors and can be coupled with surgical procedures and as a sensitive early detection probe for small tumors.

Multiple efforts from the KI have been targeted at improving known therapies. The Hemann and Chen laboratories used a humanized rodent model of B-cell leukemia to describe mechanisms underlying tumor resistance to antibody-based immunotherapy [3]. By using a combination chemoimmunotherapeutic regimen, researchers were able to sensitize tumor sites and overcome resistance. In a separate effort, the Wittrup, Irvine, and Yaffe laboratories also enhanced immunotherapy by using an antitumor antibody and a modified cytokine [4]. The combined regimen was synergistic, activating both adaptive and innate arms of the immune system to target and destroy tumors in multiple rodent models. The Hammond and Yaffe laboratories reported a timed-release nanoparticle system that maximized synergistic effects between two different chemotherapeutic drugs (Figure 3) [5]. Staggering the release of two different drugs from the same nanoparticle formulation enabled the researchers to use the first drug to sensitize targeted cancer cells to the effects of the second drug. The Manalis and Jacks laboratories collaborated to use a special device called a suspended microchannel resonator to study the cellular biomechanics of metastatic cells [6]. This approach established that cancer cells may owe their metastatic potential to enhanced deformability and reduced friction that allows them to more easily traverse tight spaces. This technology holds promise for both early tumor detection and surgical removal of deep tumors. Implantable devices can also have a role to play in cancer therapy, and the Langer and Cima laboratories implanted a clever device that can deliver combinations of drugs and evaluate their efficacy on living tumors [7]. The device was capable of assessing the effect of 16 different drugs either individually or in combination. This device could facilitate drug therapy optimization and improve drug response prediction. The Wittrup and Hynes laboratories collaborated to identify an ideal cell-surface target for antibody-based immunotherapy of disseminated tumor cells from a panel of 35 different cell-surface proteins unique to cancer cells. The determined ideal target, an antigen called CD24, is exclusively expressed on malignant tumors, highly abundant, and functionally required for tumor colonization [8]. All of this research is the product of investigators working together, complementing their respective strengths, and asking questions/developing technologies at the interface of cancer biology and engineering.

Figure 3:

Cancer-fighting nanoparticles. (A) Cryo-TEM imaging and (B) illustration of double-whammy nanoparticles made by the Hammond and Yaffe laboratories. The particles deliver two different chemotherapeutic drugs in a sequence-controlled manner, with the first drug sensitizing cancer cells and increasing the potency of the second drug. Figure taken from Morton SW et al. A nanoparticle-based combination chemotherapy delivery system for enhanced tumor killing by dynamic rewiring of signaling pathways. Sci. Signal. 2014, 7, ra44–ra44. Reprinted with permission from AAAS.

The institute’s culture of collaboration also extends beyond its walls, evidenced by the KI’s strong relationships, both academic and industrial, by partnering with academic institutions, foundations, clinical oncology centers, and pharmaceutical companies. Two initiatives are exemplary of these efforts: the Transcend program and the Bridge Project. The Transcend program is a partnership with Janssen Pharmaceuticals that funds cancer research projects at the KI with the participation of investigators from Janssen. The program has been a successful mechanism to allow academic and industrial scientists to work together to tackle obstacles facing next-generation cancer treatments. With a similar goal, the Bridge Project is a cross-institutional effort between the KI and the Dana Farber/Harvard Cancer Center to seed collaborative research projects. The objective of the initiative is to combine the engineering and cancer biology insights from the KI with the translational expertise of clinical oncologists to “bridge” the divide between basic and translational research, leading to greater insights and technologies for cancer detection and treatment. The project works with cancer research foundations to raise money to fund ideas and project teams that are cross-institutional, with the goal of this seed money establishing a lasting collaborative effort that acquires sustainable funding. In addition to these efforts, the KI has many other projects and initiatives that are ongoing: the Frontier Research Program, the Center of Cancer Nanotechnology Excellence, the Ludwig Center for Molecular Oncology, and the Physical Sciences-Oncology Center. All have the same goal of affecting cancer research by working cooperatively with the greater research community, and these relationships are key to advancing new technologies and ideas that have an effect on cancer research.

On a personal note, being a trainee at the KI has left me culturally imprinted. As I move on to start my own laboratory, I will bring with me the very perspective that the institute is practicing every day, and I suspect so will many of my colleagues in their future careers. Behind all the technology and biology, the KI stands as an affirmation of Professor Sharp’s thesis: that a culture of collaboration and cooperation is our best hope to advance the tools and insights necessary to win the fight against cancer.