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The Path to End Cancer: From Engineering Diagnostic Technologies to Crafting Therapeutic Immune Cells

Feb. 24, 2016

Vice President Joe Biden has been charged with an exciting task to lead a “new moonshot” initiative to “end cancer as we know it.”  In this mission, he will seek to marshal resources to fight cancer by having the broad community of cancer fighters work even more closely together, share information, and focus on the most promising advances in a concerted effort to end the disease. “Several cutting-edge areas of research and care — including cancer immunotherapy, genomics, and combination therapies — could be revolutionary," Biden wrote in his personal Medium blog post. This immediately followed the President’s announcement of Biden's new assignment during his final State of the Union address on Jan. 12, 2016. Biden subsequently further explained, "Innovations in data and technology offer the promise to speed research advances and improve care delivery."  

Chromosome instability in primary breast cancer cells

Unstable chromosomes in breast cancer cells. Credit: T. Reid, NCI Center for Cancer Rsch

As recognized by Vice President Biden, there is a promising role for the implementation of engineering principles and technological innovations to create novel treatments for many diseases including cancer.  Engineering immune cells for example, is a rapidly emerging field that offers great potential for therapeutic applications in cancer. Engineering allogenic immune cells to carry out controlled and targeted functions in their natural environment using gene editing tools such as CRISPR/Cas9, the production of Chimeric Antigen Receptor (CAR)-T cells that can be engineered to target any tumor antigen, and understanding the molecular mechanisms that can bypass the natural inhibitors of immune response (e.g. anti PD-1), are among the major exciting areas of bioengineering research that hold promise.

The current experimental immunotherapy vaccines isolate and reprogram immune cells outside of the body and reintroduce the cells back into the patient to induce an anti-cancer response. This process is time consuming, and has risks including chances of infection. A less cumbersome and more effective approach to elicit a strong targeted immune response is desirable. Bioengineering tools such as self-assembling nano-biomaterials provide cutting-edge methods to explore effective ways to tackle these challenges. For example, David Mooney, a bioengineer at Harvard University, is currently developing antigen labelled nanoparticles that can be injected into the body and, after self-assembly into a matrix, recruit host dendritic cells that generate a potent response that in turn targets breast cancer in animal models. In this approach, the biomaterial mimics a bacterial infection, harboring tumor antigens that effectively attract dendritic cells capable of stimulating specific T-cell populations that target the breast cancer cells.

Early detection of cancer is another promising area of cancer research that can save millions of lives by providing the opportunity for more curative interventions. Improved screening increases the chances of detecting certain cancers early, when treatments are most effective. Former President Jimmy Carter’s metastatic melanoma is in remission as a result of a recent FDA approved immunotherapy drug Pembrolizumab, also known as “Keytruda”, which is used after early detection of metastatic melanoma lesions. This underscores a great need for routine procedures capable of early detection.

Modern cancer care includes screening (e.g., mammography, colonoscopy), molecular diagnostics, targeted treatment, and follow-up using imaging technologies that can help accurately characterize the disease at the molecular, cellular, and organ levels. Emerging devices that can isolate circulating tumor cells (CTCs) before these form a detectable tumor will be tremendously valuable. Mehmet Toner, from Harvard Medical School is currently refining an iChip technology that captures and analyzes CTCs from a patient’s peripheral blood when they are extremely rare (less than 1 per billion normal cells) and before a tumor may be clinically evident. This project couples CTC isolation with single cell RNA analysis of the cells to detect and characterize cellular heterogeneity, and track the constant mutations. This promises to provide a system for more clearly identifying the most effective treatment and/or tracking the patient’s progress.

The next step for iChip development is miniaturization to construct a “Point of Care” device that can be made available in clinics and health centers in rural areas. This is an exemplar of convergence research in which bioengineering interfaces with cancer biology and other areas of science such as immunology, to tackle daunting challenges. The promising solutions range from engineering cells, genes and proteins to developing technologies that are readily available to all patients, inclusive of those in the lowest resource settings. As Vice President Biden stated in his Medium post, "It's not just about developing game-changing treatments — it's about delivering them to those who need them."

Authors: Shadi Mamaghani (PhD) and Roderic I. Pettigrew (PhD, MD)