A former Model T factory builds the next generation of cancer treatments
Caption: The Ford plant in Pittsburgh assembled up to 40 Model Ts a day through the early 1930s. Ford’s Highland Park, Michigan, plant (shown here) was of the same design. (Photo courtesy The Henry Ford)
A century ago, an imposing multistory building in Pittsburgh’s East End became one of the nation’s first Model T Ford assembly plants, lifting materials from rail tracks below to fabricate cars from the top floor down.
Today, that same building has been transformed through a $330 million investment by the University of Pittsburgh for a new kind of construction—creating tailor-made treatments to combat cancer and other diseases.
Appropriately named The Assembly, the eight-story building at Baum Boulevard and Morewood Avenue will house scores of researchers largely devoted to cancer.
The building, which later housed a clothing factory and a stationery store, sits just a block away from the flagship UPMC Hillman Cancer Center building, and expands the center’s research space by 50%, says Robert Ferris, Hillman Professor of Oncology and Hillman director.
“It’s very fortuitous to find a place right nearby in such a crowded neighborhood,” he says.
“Both Bob and I are extremely excited about the ability to move into this new space,” adds Dario Vignali, Distinguished Professor of Immunology and interim chair of Pitt’s Department of Immunology, whose scientists will have a major footprint at The Assembly.
The building is filled with references to its automotive history, from vintage photos in the elevators to a 4 1/2-story atrium known as the crane shed, which occupies the space where cranes used to lift raw materials off train cars and deposit them on platforms that fed into the different floors.
Those loading platforms have been repurposed into balcony meeting spaces that look down on the crane shed, which overlooks the East Busway.
The Assembly’s architects created spaces where researchers from different disciplines can meet to share results, ideas, food—the master plan is to foster serendipity.
All told, the existing five floors of labs can accommodate more than 600 scientists.
“At the end of the day, the reason why this building is going to be successful is what always makes science successful: people,” says Greg Delgoffe, associate professor of immunology and director of the Tumor Microenvironment Center, whose labs have moved to The Assembly. “The whole point of this beautiful, historic place is that it brings together a number of really important sets of researchers.”
Computational biology groups at The Assembly (check out the “Seeing Patterns” sidebar) will help power discovery. Among other feats, those scientists are able to compare and contrast patient genomes. “The question we’re often trying to answer is, ‘Why does one person clear the tumor when another person is unresponsive?’” says Vignali.
The Assembly will also pull in cancer researchers from Magee-Womens Research Institute, including Adrian Lee, the Pittsburgh Foundation Professor of Precision Medicine, and Steffi Oesterreich, Shear Family Professor of Breast Cancer Research and codirector of the Women’s Cancer Research Center. The two are making important advances in the genetic study of breast cancers and their treatments. (See “What does the patient really need?” also in this issue.)
And while there are no spinoff companies located in the building now, such tenants could move in as commercialization opportunities emerge from the research under way, Ferris and Vignali say. That would add to the roster of cancer startup firms these groups have already generated, such as BlueSphere Bio, cofounded by former immunology chair Mark Shlomchik; BlueSphere is creating individualized T cell therapies. Another startup, Novasenta, founded by Delgoffe, Ferris and Vignali, develops detailed analyses of human tumor samples to seek new therapeutic targets.
When Delgoffe reflects on the history of the building, he notes that the point of the Ford plant was to end up with a car that someone could drive out of the first-floor showroom.
“What was the problem the Ford assembly building had to tackle? You needed to be able to concentrate your efforts and create something that could roll off the floor and be used.” In the same way, The Assembly will look at the raw materials of cancer with the goal of developing treatments that can be driven off the lot.
Some of the in-house researchers study the basic mechanisms of how bodies react to cancer; others test new approaches in animal models and conduct clinical trials.
“So it’s really soup to nuts,” Delgoffe says, “thinking about basic understanding of cancer coupled with folks who are trying to translate that into the clinic.”
Better, stronger T cells
The newest approaches to treating cancer rely on the body’s immune system rather than the blunter instruments of chemotherapy and radiation.
An impressive example from recent years has been CAR T cell therapy—in which a patient’s immune system T cells are engineered in the lab to seek out cancer in the body. The approach has worked well against blood cancers like leukemia but hasn’t had much success in solid malignancies like liver and colorectal cancer.
That’s a challenge Greg Delgoffe’s lab is tackling. One reason T cells don’t function very well in solid cancers, he says, is that the microenvironment inside those tumors has very little oxygen or few nutrients. Those substances are consumed quickly by the proliferating cancer cells.
That impoverished landscape hinders the activity of the T cells, Delgoffe says, and they can become exhausted and lose their potency.
His lab is exploring ways to restore vitality to T cells so they can work just as well inside those tumors as they do in the bloodstream.
“With CAR T cell therapy,” he says, “you genetically engineer the T cell to see the cancer. Our take is while we’re redirecting T cells in that way, why not ‘load them up’ to be able to produce more energy? In other words, can we build a better CAR T cell that is designed to weather the storm and persist in that toxic tumor environment?” —Mark Roth
The Richards Auditorium
In October, The Assembly’s auditorium was named in honor of the late Thomas Richards, chair of the University Board of Trustees at the time of his death in 2021. “This will be a place to disseminate new knowledge and generate collaborative approaches to high-risk, high-reward research questions,” noted Dean Anantha Shekhar. “It is where we will convene for major scientific meetings and other events. It’s an important space.”
With tens of thousands of molecular factors at play just in the human genome, how can scientists make sense of the genetic landscape of cancer and the immune system?
Harinder Singh, whose experimental and computational biology group will be housed in The Assembly, says researchers are increasingly using machine learning approaches to find molecular patterns underlying certain cancers or autoimmune diseases—patterns that are too complex for any human to see. But the computational tools can’t reveal disease mechanisms or how to target them. That’s where the creative work comes in.
The professor of immunology and director of the Center for Systems Immunology says, “Machine learning is very good at predicting features” of biological processes, but it “is not able to interpret those features. For that, we still need human intelligence to come up with these causal explanations, which we can then experimentally test.” —Mark Roth