Our goal is to discover new ways to stimulate the immune system to treat cancer. We study pancreatic cancer, a model deadly cancer that is refractory to all immunotherapies, as well as nearly all other treatments. We use reverse translation to uncover the biological basis of exceptional response in rare survivors of pancreatic cancer, discover underlying mechanisms in model systems, and accelerate insights to new immunotherapies for patients.
We discovered natural anti-tumor immunity in rare long-term survivors of pancreatic cancer (Balachandran et al., Nature 2017; Łuksza et al. Nature 2022). In these patients, CD8+ T cells spontaneously recognize somatic mutation-derived neoantigens to impart long-lasting anti-tumor immunity. This finding challenged the prevailing assumption that pancreatic cancer, like most solid tumors, lacks clinically relevant neoantigens and is thus immunologically inert, sparking our efforts to “therapeutically phenocopy” the exceptional survivor state. Aligned with this, we have identified and continue to study two complementary strategies to augment immunity in pancreatic cancer: (1) enhance neoantigen-specific immunity with cancer vaccines, and (2) induce a “lymphoid state” that supports anti-tumor CD8+ T cell function in the tumor microenvironment. As pancreatic cancer is a prototype immunotherapy-insensitive cancer, we aim to establish fundamental principles in pancreatic cancer that can serve as blueprints for other immunotherapy-insensitive cancers.
Precision cancer vaccines: Based on our discovery of clinically relevant immunogenic neoantigens in long-term pancreatic cancer survivors, we are investigating individualized neoantigen vaccines as a novel therapy for pancreatic cancer (Rojas et al. Nature 2023; Sethna et al. Nature 2025).
We pair iterative precision clinical trials with deep science in vaccinated patients, with the goal to establish next-generation vaccination paradigms with enhanced accuracy, potency, utility, and durability. To achieve this, we work closely with The Olayan Center for Cancer Vaccines (OCCV) at MSK, a one-of-a-kind biohub with end-to-end capability to design, manufacture, administer, and iteratively improve cancer vaccines in-house.
Lymphoneogenesis: In complementary work to activate immunity in pancreatic cancer, we discovered a new potentially druggable pathway of inducible lymphoneogenesis (Moral et al. Nature 2020; Amisaki et al. Nature 2025). We utilize mouse models and human samples to define the cells and molecules of this lymphogenic pathway and use these mechanistic insights to develop new testable immunotherapies for patients with pancreatic cancer.