PROFILE to grants,” she said. “As a scientist, you also want to be creative, and it’s the same for figure skating. You have to have a creative program in addition to jumping and the technical [aspects], but also, the delivery.” In 2010, she started her own group at Case Western Reserve University School of Medicine, focused on molecular engineer-ing of bio-inspired nanotechnologies. She decided to explore a few different plant viruses that could be used for drug delivery: tobacco mosaic virus (TMV), potato virus X (PVX), and cow-pea mosaic virus (CPMV), which infects black-eyed pea plants. She leveraged bionanoparticles, also known as viral nanopar-ticles (VNPs), from these viruses as tools for cargo delivery. 1 A special feature of these plant viruses is that they interact with mammalian cells without infecting or replicating; instead, cells engulf the viruses and recognize them as foreign, which prompts an immune response. First, Steinmetz investigated how their distinct features, such as differences in morphology, could support drug deliv-ery. For instance, some shapes enable cargo to be loaded either internally or externally while size affects the payload amount. As TMV is one of the most studied plant viruses, she used it as a reference point for comparison. It has a long, rigid shape. PVX is a less studied subject and boasts a unique shape. Most other particles are spherical or rod-shaped, and often these tend to be short molecules. “But the potato virus acts almost like spa-ghetti. It’s very long and filamentous,” said Steinmetz. I think there are a lot of parallels with being an athlete in general and being a scientist. —Nicole Steinmetz, University of California, San Diego Steinmetz conducted comparative studies in which she tagged different particles with distinct colored dyes and injected them into an animal to observe the particles’ behav-ior. The results revealed striking differences. “We very quickly realized that they all behave totally differently,” she explained. “Even viruses that come from the same plant…they have differ-ent strengths and weaknesses for different applications.” Due to their elongated shape, Steinmetz noted that TMV and PVX were better at delivering cargo somewhere within the body. However, CPMV, which is icosahedral shaped, produced an unexpected result. When delivering a drug to cancer cells in mouse models, Steinmetz and her team found the expected empty particles afterward, indicating that the cargo had been successfully released. 2 The drug-loaded CPMV reduced tumor growth; however, analysis of the tumor growth curves revealed that the empty, drug-free CPMV also exhibited a subtle yet mea-surable effect. This suggested that the native CPMV influenced the tumor in some manner. Steinmetz explained, “We reasoned 16 THE SCIENTIST | the-scientist.com that it’s probably [got] something to do with the immune sys-tem, but we…didn’t look at this from the right angle.” Soon after, around 2014, Steinmetz met Steven Fiering, an immunologist and cancer biologist at Dartmouth University, at a conference. Fiering was studying intratumoral immuno-therapy, an approach based on the idea that tumors are immu-nosuppressive and can be manipulated to become immunos-timulatory, thereby generating antitumor immune responses—a strategy described as in situ vaccination. Fiering used bacteriophages to treat cancer cells as one approach. He struggled with reducing the amount of lipopolysac-charide (LPS) contamination in his phage preparations. When he attended Steinmetz’s talk on plant viruses, she noted that plant viruses are generally LPS-free because they are derived from plants. This immediately caught Fiering’s attention. He had never considered using plant viruses for cancer therapy previously, but Steinmetz was enthusiastic about the idea, he recalled. Steinmetz added, “Everything sort of was aligned. We already had some data and some clues.” They planned to study all the plant viruses in Steinmetz’s arsenal, but because Fiering did not have a license from the United States Department of Agriculture to work with infectious plant viruses in his lab, they had to improvise. Stein-metz provided him with versions of CPMV that lacked RNA and were therefore noninfectious to plants. This quick solution also ended up being a serendipitous choice for their project. CPMV produced promising results, while starting with other particles might have discouraged the team from continuing. Building on Steinmetz’s earlier observations, the duo collab-orated to discover that inhalation of CPMV nanoparticles pro-duced anti-tumor effects in a lung melanoma and ovarian can-cer mouse model. 3,4 “Sometimes, it’s the things that don’t work exactly as we think they should be working, those are in fact the most interesting ones,” Steinmetz said. It was pure luck, Fiering said. They found that, compared to other plant viruses, such as TMV and PVX, CPMV was significantly more effective, though the researchers still did not fully understand why. Fiering remarked, “She recognized plant viruses as their own interesting biological niche,” and she leveraged these malleable viruses for different applications. “She’s remarkable. She’s a very exceptional scientist that I’ve been very fortunate to work with for the past 10 years.” Cowpea Mosaic Virus: An Unexpected Cancer Vaccine Candidate Although Steinmetz did not have formal immunology training, she and Fiering continued to further investigate plant viruses as an in situ vaccine therapy. CPMV showed promising prelim-inary results, but the exact mechanism behind its success was still a mystery. Over the next decade, Steinmetz and her colleagues dug deeper. They found that the CPMV nanoparticles, while not infectious to mammalian cells, can be taken up by immune cells. There, Toll-like receptors recognize them as foreign. So,
The Scientist Spring 2026: Page-16
