Parker Institute for Cancer Immunotherapy

Some of cancer's most revealing signals arise not from precision, but from error. In a new PICI-funded study, published in Cancer Cell by Cell Press, PICI Investigator and co–first author Chris McGinnis, PhD (Stanford), and a collaborative international research team uncover how eliminating a single enzyme can flip tumors from hidden threats into visible immune targets. The research, conducted while Dr. McGinnis was a 2023 Parker Scholar in the lab of Ansuman Satpathy, MD, PhD, Co-Director of the PICI Center at Stanford University School of Medicine, reveals a novel link between translational stress and immune recognition. The concept: Removing TYW2—a Phe-tRNA–modifying enzyme—disrupts the normal protein-building process. Without it, ribosomes stall when translating phenylalanine codons, introducing “frameshift” errors. These mistakes scramble the resulting proteins, producing abnormal peptides that the immune system can more easily detect—essentially turning tumors into visible targets. Key takeaways: → Knocking out TYW2 throws off the protein-building process, creating abnormal peptides that can act like distress signals for the immune system. → These peptides help CD8? T cells better recognize and attack cancer cells. → In patients with melanoma, tumors with less TYW2 tend to respond more effectively to checkpoint inhibitor therapies—and those patients tend to live longer. Why it matters: → This approach may offer a new way to help patients whose tumors don’t respond to existing immunotherapies. → It could turn “cold” tumors—those that normally hide from the immune system—into targets the body can fight. → TYW2 levels might help predict which patients are more likely to benefit from immunotherapy. Congrats to the international research team behind the study—this work is a compelling reminder that even cellular chaos can reveal powerful therapeutic insights. → Read the full study in Cancer Cell: https://lnkd.in/gBZy7wg6 #CancerResearch #Immunotherapy #TranslationalScience #PICI

Three patients remain completely tumor-free five years after receiving PGV001, a personalized multi-peptide neoantigen vaccine aimed at preventing cancer recurrence. These remarkable long-term outcomes, recently published in Cancer Discovery, emerge from a Phase 1 study just completed by PICI Investigator and AACR Fellow Bhardwaj Nina, MD, PhD, Director of Immunotherapy at the Icahn School of Medicine at Mount Sinai. The trial enrolled 13 patients at high risk of relapse after initial treatment for diverse cancer types. At the five-year mark, six of the 13 participants (46%) remained under observation, including three with no evidence of cancer. Overall, seven participants did not reach the five-year endpoint, primarily because of cancer progression. Key findings: → Strong immune activation: 100% of vaccinated patients developed targeted immune responses, demonstrating the potential of PGV001 to safely induce tumor-specific immunity, even in high-risk populations and across multiple cancer types. → Broad applicability: Clinical benefit was observed across diverse cancer types, including non-small cell lung cancer, head and neck cancer, urothelial cancer, breast cancer and multiple myeloma. → Favorable safety profile: PGV001 showed no serious adverse effects, with only mild injection?site reactions reported. Why it matters: → The durability of responses at the five-year mark suggests potential long-term protection against cancer recurrence. → Personalized vaccines like PGV001 train the immune system to recognize unique cancer mutations, enabling more precise targeting of malignant cells. → This approach has particular promise for patients at high risk of recurrence after initial treatment. Learn more: → Explore the full study in Cancer Discovery: https://lnkd.in/dG-yAHaU → Listen to an episode of PICI’s podcast “From Bench to Fireside” featuring Dr. Bhardwaj: https://lnkd.in/dcdXfhRU → Read Mount Sinai’s press release: https://lnkd.in/dFAdwgid #PICInetwork #CancerVaccines #Immunotherapy #Oncology #CancerTreatment

Listening to From Bench to Fireside this season? If you're not subscribed to PICI's podcast, you're missing some of the most consequential conversations in cancer research this year. From Bench to Fireside brings together the pioneers who are reshaping cancer treatment—turning cutting-edge science into real patient impact. These aren’t just interviews—they’re insider discussions on the breakthroughs reshaping immunotherapy. Carl June, MD, the "father of CAR T therapy," takes us inside the next frontier of cellular therapy and CRISPR-driven cancer treatments. Antoni Ribas, MD, PhD, shares how immunotherapy has transformed melanoma treatment, achieving five-year survival rates of up to 50% for many patients who respond to these therapies.?Elizabeth Mittendorf, MD, PhD, a breast cancer research trailblazer and American Society of Clinical Oncology (ASCO)'s incoming President, unpacks how collaboration is fueling the next wave of patient impact. Roberta Zappasodi, PhD, breaks down how tumors hijack metabolism to disarm immune cells—and how researchers are fighting back. Cancer research doesn’t happen in isolation.?These conversations show how PICI’s model unites top scientists to tackle cancer’s toughest challenges – driving progress faster than any one institution could. Catch up this weekend: → From CAR T-Cell Therapy to the Impact of Mentorship – Carl June, MD, Director of the PICI Center at the University of Pennsylvania → From Metastatic Melanoma to Immune Engineering – Antoni Ribas, MD, PhD, Director of the PICI Center at UCLA → From the Front Lines to the Frontiers of Defeating Breast Cancer – Elizabeth Mittendorf, MD, PhD, Co-Director of the PICI Center at Dana-Farber Cancer Institute → From Cancer's Hidden Metabolic Tricks to Breakthrough Discoveries – Roberta Zappasodi, PhD, PICI investigator at Weill Cornell Medicine, 2016 Parker Scholar and 2019 Parker Bridge Fellow ???Apple Podcasts: https://lnkd.in/gKBZuSKV ??? Spotify: https://lnkd.in/gwE3M9bb #CancerImmunotherapy #BenchToFireside #Podcast

Please join PICI in celebrating Owen Witte, MD, Co-Director of the PICI Center at UCLA, recipient of the 2025 Harrington Prize for Innovation in Medicine in recognition of his extraordinary contributions to cancer research and treatment. Dr. Witte’s discoveries have helped transform modern oncology. His foundational research in tyrosine kinase inhibitors enabled the development of Gleevec and ibrutinib, two targeted therapies that have significantly improved treatment for leukemia and lymphoma. In prostate cancer research, his co-discovery of the prostate stem cell antigen (PSCA) identified a potential therapeutic target, guiding efforts to develop more precise treatments, including novel immunotherapies. His ongoing work in epithelial cancer stem cells continues to inform strategies for advancing next-generation cancer therapies. As part of this honor, Dr. Witte will deliver the Harrington Prize Lecture at the AAP/ASCI/APSA Joint Meeting (April 25-27) and speak at the Harrington Scientific Symposium (May 21-22), sharing insights from his decades of cancer research. A key leader in the PICI Network, we honor Dr. Witte for his relentless drive — not stopping when a question is answered or a problem solved, but pushing science further to achieve results that truly matter for patients. #HarringtonPrize #CancerResearch #Immunotherapy

Hot off the press! The mid-March edition of The Immuno-Oncology Digest features notable advances in cancer #Immunotherapy from across the PICI Network. Not receiving these updates because you haven’t subscribed yet? Here are seven key developments shaping cancer treatment this month: 1. BEANIE Computational Tool: Dana-Farber researchers, led by Eliezer Van Allen, MD, have developed a platform that enhances tumor progression tracking and supports precision oncology applications. 2. Nonviral CRISPR Engineering: Stanford's Theodore Roth, MD, PhD, and Ansuman Satpathy, MD, PhD, Co-Director of the PICI Center at Stanford, have introduced an intron knock-in method that preserves gene function while expanding cellular therapy possibilities. 3. CAR-T Safety Analysis: Carl June, MD, Director of the PICI Center at the University of Pennsylvania, and team share a review that confirms the strong safety profile of CAR T therapies after a decade of clinical application. 4. Tumor Metabolism Research: Weill Cornell Medicine’s Roberta Zappasodi, PhD, examines how tumors manipulate metabolism to evade immune responses—featured in our latest podcast. 5. NK Cell Signaling Insights: UCSF investigators, including Lewis Lanier, PhD, founding PICI Center Director, and Justin Eyquem, PhD, have identified regulatory mechanisms that could improve CD19-CAR NK cell efficacy against resistant malignancies . 6. T Cell Exhaustion Mechanisms: A Penn Medicine research team, led by E. John Wherry, Co-Director of the PICI Center at Penn, explores how TOX expression influences T cell function, with implications for improving immunotherapy durability. 7. Advanced CRISPR Protocol: A new peptide-enabled delivery system streamlines cellular engineering for next-generation immune therapies. The digest also highlights recent honors for PICI investigators, including AACR Academy Fellows induction and Emerging Leader recognition. →Subscribe to receive future issues directly: https://lnkd.in/dEm2qHz → Read the latest now, and then share with a friend: https://lnkd.in/dH_QVgZN #CancerResearch #PICInetwork

CAR T-cell therapy isn’t just a breakthrough—it’s a lifeline. A new review in Molecular Therapy by Carl June, MD, Director of the PICI Center at the University of Pennsylvania, and colleagues Kisha K. Patel, Mito Tariveranmoshabad, Siddhant Kadu and Nour Shobaki—supported by PICI—traces the decades of research, challenges and discoveries that transformed engineered immune cells into a powerful cancer treatment. For every patient who has asked, “What else can we try?” CAR T is proof that bold, collaborative science delivers real-world impact. Key takeaways: → From Concept to Reality: After years of research, the first FDA?approved CAR T therapy for leukemia in 2017 proved that reprogrammed T cells could effectively target and eliminate cancer. → Expanding Reach: CAR T is now being tested in clinical trials for solid tumors like glioblastoma and prostate cancer, tackling some of the toughest challenges in oncology. → Improving Safety: Advances in gene editing, including CRISPR, are refining CAR T therapy to reduce risks like cytokine release syndrome (CRS) and neurotoxicity while enhancing long?term effectiveness. → Scaling for More Patients: Manufacturing CAR T-cells remains complex and costly. PICI?backed efforts are advancing off?the?shelf and mRNA?based approaches to make these therapies more widely available. → Next?Gen CAR T: Smarter, more persistent CAR T-cells targeting multiple antigens, resisting exhaustion and better navigating the tumor microenvironment are moving the field toward broader, lasting impact. More than a pioneer, Dr. June—”the father of CAR T-cell therapy”—helped lay the groundwork for a treatment that is reshaping cancer care. And with the PICI Network driving the next generation of innovation, we remain relentless in our mission to turn all cancers into curable diseases. → Read the full review in Molecular Therapy: https://lnkd.in/gRFtYdHP → Behind the Breakthrough – Dr. June on CAR T’s impact: https://lnkd.in/gdXKZb8n → From Bench to Fireside – Dr. June on mentorship and discovery: https://lnkd.in/gnric7im #CancerResearch #Immunotherapy #GeneEditing #CellTherapy

PICI is honored to be a beneficiary of the 7th Annual Emerging Frontiers in Oncology! On May 22 in Cambridge, MA, PICI CSO John Connolly, PhD, will join esteemed leaders in #biotech and #oncology to explore this year’s theme: "Investing in Oncology: Aligning Stakeholders Amid Shifting Perspectives." In a fireside chat with Uciane Scarlett, PhD, Dr. Connolly will discuss the forces driving change in the field and the breakthroughs on the horizon. A portion of the proceeds will directly support PICI’s mission to turn all cancers into curable diseases. Check out the full agenda and register: https://lnkd.in/gCfAcBX

Congratulations to PICI Network Investigators Bhardwaj Nina, MD, PhD, Director of Immunotherapy at the Icahn School of Medicine at Mount Sinai, and Robert H. Vonderheide, MD, DPhil, Director of the Abramson Cancer Center at the University of Pennsylvania, for their outstanding recognition as 2025 Fellows of the?American Association for Cancer Research Academy! This distinction honors an elite tier of cancer researchers and recognizes Drs. Bhardwaj and Vonderheide’s transformative immunotherapy contributions that are redefining patient care. Drs. Bhardwaj and Vonderheide’s achievements exemplify PICI’s commitment to bold, collaborative research, and bring us closer to making every cancer curable. We’re proud to celebrate their relentless dedication to advancing treatment and improving lives worldwide. #AACRFellows

We're excited to share this new seminar series hosted in partnership with the Gladstone-UCSF Institute of Genomic Immunology and Parker Institute for Cancer Immunotherapy!

?? NEW FROM BENCH TO FIRESIDE: Tumors stack the odds in their favor—hoarding nutrients and starving immune cells of the energy they need to fight back. But researchers are finding ways to outsmart cancer’s metabolic advantage. In our latest podcast episode, PICI Investigator Roberta Zappasodi, PhD, Assistant Professor of Hematology and Medical Oncology at the PICI Center at Weill Cornell Medicine, joins PICI’s Chief Scientific Officer, John Connolly, PhD, to explore how cancer’s metabolic tricks create roadblocks to immunotherapy—and how her lab is developing new strategies to fuel T cells for the fight. A 2016 Parker Scholar and 2019 Parker Bridge Fellow, Dr. Zappasodi has been at the forefront of immunotherapy research—from her early work preparing vaccines from tumor samples to her groundbreaking discoveries on how tumor metabolism and vasculature impact treatment response. Tune in to hear:? → How tumor metabolism and vasculature impact immunotherapy success →? Why moving immunotherapy to earlier treatment stages could improve outcomes → How multi-disciplinary collaboration is driving new discoveries Listen now:? → Apple Podcasts: https://lnkd.in/eddc8wud → Spotify: https://lnkd.in/eVuJq9Yv #CancerImmunotherapy #ImmunotherapyResistance #SciencePodcast