In a short time, the 2018 AAPS Emerging Leader Award recipient has accumulated an impressive list of accomplishments.
By Linda C. Brown
James J. Moon, Ph.D., received the 2018 AAPS Emerging Leader Award. When he joined the University of Michigan Department of Pharmaceutical Sciences as an assistant professor in 2012, Gordon L. Amidon, Ph.D., was impressed with how quickly Moon hit the ground running on day one. Since then, he has raised $5.3 million in external funding, received numerous national and international awards recognizing his contribution to pharmaceutics and cancer immunotherapy, and published in highly acclaimed journals. “Simply put, he is a remarkable scientist who has already made great scholarly contributions to the field of drug delivery and nanomedicine, and he is on track to become a leading authority in the field of pharmaceutical sciences,” says Amidon. Moon is now John Gideon Searle Associate Professor in the Department of Pharmaceutical Sciences and Biomedical Engineering at the University of Michigan.
The Science
Moon has made outstanding contributions to the field of drug delivery by developing new nanoparticle systems for enhancing immune functions. His interdisciplinary research program aims to develop novel biomaterials-based strategies to advance fundamental understanding of the immune system and to modulate immune functions, all to produce effective vaccines and cancer immunotherapies to improve patients’ lives. His innovative research has led to a new class of vaccine nanoparticle system that can elicit unprecedented levels of T- and B-cell immune responses.
Moon reports, “My lab has shown for the first time that nanovaccines can be tailored to each cancer patient’s unique tumor mutations, thereby serving as a potent platform to generate antitumor T-cell responses that cannot only eliminate established tumors but also confer long-term protection against tumor recurrence. This is an important step in our field; it demonstrates the feasibility of personalized cancer immunotherapy using nanovaccine formulations.”
As a result, Moon’s work has generated broad interest, and he has founded a new biotech startup, called EVOQ Therapeutics, to expedite translating the discovery from preclinical studies to clinical trials.
As Moon describes his work, recent innovations in DNA/RNA sequencing have enabled identifying patient-specific tumor neo-antigens. Peptide vaccines in general may serve as an ideal platform for neo-antigen vaccines, but peptide vaccines have shown limited therapeutic efficacy in clinical trials. Moon’s work presents an alternative strategy where preformed nanodiscs based on synthetic high density lipoproteins, with an established clinical manufacturing procedure and excellent safety profiles in humans, are readily formulated with adjuvants and antigen peptides. “We show that these nanodiscs can efficiently deliver immunostimulatory molecules and antigens, including neo-antigens to drain lymph nodes. Notably, nanodiscs elicited up to 47-fold greater frequency of tumor neoantigen-specific CD8+ T lymphocytes (CTLs) than soluble vaccines in mice, and even 31-fold greater than the standard adjuvant in clinical trials (i.e., CpG in Montanide),” he says.
He reports that when nanodisc vaccine was combined with anti-PD-1 immune checkpoint inhibitor, ~88% complete response was observed in MC-38 tumor-bearing mice, compared with 25% response rate in the control group receiving soluble vaccine plus anti-PD-1 therapy. In a more aggressive B16F10 melanoma model, nanodiscs delivering multiple MHC class I and class II neo-epitopes were combined with α-PD-1/α-CTLA-4 therapy, leading to ~90% complete response in B16F10 tumor-bearing mice, compared with ~38% response rate in the control group with soluble vaccine plus α-PD-1/α-CTLA-4 therapy.
“Furthermore,” Moon says, “we have demonstrated the efficacy of nanodisc technology using shared tumor antigens in murine models of HPV+ mucosal tumors. The reproductive tract tumor model was established in C57BL/6 mice by intravaginal administration of luciferase-expressing TC-1 cells, a surrogate for HPV-induced human tumors such as cervical carcinoma. The lung metastasis model was established by intravenous injection of luciferase-expressing TC-1 tumor cells. In mice bearing intravaginal or lung TC-1 tumors, two nanodisc vaccinations with HPV16 E7 antigen generated the peak frequency of ~35% tetramer+ CTLs in peripheral blood and eliminated established TC-1 tumors in the majority of animals (without immune checkpoint blockade). Owning to the facile production process, robust therapeutic efficacy, and good safety profiles, our nanovaccine technology offers a powerful and convenient platform for vaccination using personalized as well as shared tumor antigens.”
“These are clearly high risk/high reward areas that require extensive expertise in a wide range of disciplines, including pharmaceutics, vaccine design, cancer biology, and immunology,” says James T. Dalton, Ph.D., dean and professor of pharmaceutical sciences at the University of Michigan. “Dr. Moon’s interdisciplinary training, outstanding personal qualities, and innovative approach to problem solving make him uniquely prepared to leverage Michigan’s research ecosystem and address these important medical challenges.”
Leadership
In less than six years from his start as an assistant professor at the University of Michigan, Moon has “established an outstanding research program with wide recognition,” says Amidon. “He has already assembled top scientists in this field and has started key collaborations.”
Moon believes that leaders should have a strong vision for their organization. “I seek to understand what the unmet medical needs are and how one can achieve these goals,” he says. “I believe innovation is a crucial component that sets you apart and propels your approach to problem-solving.”
In addition, Moon believes that a good leader should be able to listen to and recognize the needs of other parties. A good leader should also engage the team to understand its members and their strengths and weaknesses to maximize their potential.
Success
“Making the most innovative strides in science always takes extra effort and time, but it’s very much worth it,” Moon says. He is happy to have found his scientific niche, which focuses on using the latest technologies to drive innovations in drug development.
Among Moon’s strong publication record, both Amidon and Dalton point to his 2017 publication in Nature Materials on his innovative approach to translational medicine, marrying new biomaterials design and vaccinology to arrive at a breakthrough technology for personalized cancer immunotherapy.
“His lab showed for the first time that nanovaccines could be tailored to each cancer patient’s unique tumor mutations, thereby serving as a potent platform to generate antitumor T-cell responses that can eliminate established tumors and achieve long-term protection against tumor recurrence,” says Dalton. “This is a breakthrough in the field of drug delivery that demonstrates, for the first time, personalized nanomedicine for cancer immunotherapy.”
“I have always been fascinated by how medicines work and always wanted to develop new drugs to benefit patients,” Moon says. “It is quite a privilege to work on something that I feel passionate about.”
He urges those pursuing a career in the pharmaceutical sciences to “find your passion and pursue that dream. It is a great privilege for me to be able to work on something that I truly care about and enjoy doing!”