Parker Institute for Cancer Immunotherapy

For eight years, the Parker Institute for Cancer Immunotherapy has united leading investigators and research institutions through the PICI Network, advancing breakthroughs in cancer immunotherapy. In 2024, this momentum reached new heights, driving bold scientific progress and transforming discoveries into therapies that are already reshaping cancer care and improving lives. This year’s achievements underscore the strength of collaboration—turning cutting-edge research into real impact for patients. The PICI Network continues to push boundaries, proving the effectiveness of our model in tackling some of cancer’s toughest challenges. Watch our highlights video to reflect on this year’s impact and the bold work ahead. For a deeper dive, explore The 2024 PICI Impact Report and learn how these achievements are advancing progress for patients and setting the stage for future breakthroughs. Thank you for your continued support. We look forward to building on this momentum together in 2025! → Read the 2024 PICI Impact Report: https://lnkd.in/g-ZmTsvs #CancerImmunotherapy #TurningCancerIntoCures

Please join us in congratulating Elizabeth A. Mittendorf, MD, PhD, MHCM, FASCO, Co-Director of the PICI Center at Dana-Farber Cancer Institute, on her election as ASCO President for 2026-2027—an incredible recognition of her leadership in cancer research and care! Read more: https://brnw.ch/21wPuRW

Don't miss PICI Chief Scientific Officer John Connolly, PhD, as he joins distinguished panelists Janet Woodcock, MD (former Principal Deputy FDA Commissioner), Paul Nghiem, MD, PhD (Fred Hutch) and George Demetri, MD (Dana-Farber Cancer Institute) for an insightful discussion on advancing clinical trials. Moderated by Endpoints News founder John Carroll. Dec. 17 at 11 am ET. Register for free and join virtually: events.endpts.com.

T cells face a fundamental challenge in cancer immunotherapy: balancing effective activation with long-term survival. A PICI-funded study just published in Nature Portfolio reveals how a protein called MED12 serves as a dynamic orchestrator, governing the critical transition between rest and activation states, offering new insights into engineering more durable T cells. The collaborative team of researchers behind the study from Gladstone Institutes and University of California, San Francisco was led by Alex Marson, MD, PhD (Director of the PICI Center at Gladstone Institutes and Director of the Gladstone-UCSF Institute of Genomic Immunology), with Maya Arce, a PhD student in the Marson Lab, as first author. The team included PICI Investigators Zachary Steinhart, PhD (2024 Parker Bridge Fellow), Nevan Krogan, PhD, Julia Carnevale, MD (Co-Director of the PICI Center at UCSF and Affiliate Investigator at Gladstone), and Ansuman Satpathy, MD, PhD (Co-Director of the PICI Center at Stanford University School of Medicine and Affiliate Investigator at the Gladstone-UCSF Institute of Genomic Immunology). Key findings: → MED12 serves as a dynamic orchestrator, precisely controlling gene networks that govern T cell state transitions → Genetic ablation of MED12 reveals a critical cellular phenomenon: T cells become trapped in an intermediate transcriptional state, unable to fully reach either a completely rested or fully activated condition → Laboratory studies showed that T cells lacking MED12 experience reduced activation-induced cell death. Why it matters: A significant limitation of current CAR T-cell therapies is the rapid exhaustion or death of T cells after activation. Understanding MED12's role opens new possibilities for engineering T cells that can persist and function more effectively in therapeutic interventions. → Explore the study in Nature: https://lnkd.in/g4AXxGaV → Read the Gladstone article: https://lnkd.in/gh5Gcn6a

Why has immunotherapy—a breakthrough that has transformed treatment for many cancers—remained ineffective for most prostate cancer patients? A research team, led by Lawrence Fong, MD, former Co-Director of the PICI Center at University of California, San Francisco, and current Director of the Integrative Immunotherapy Research Center at Fred Hutch, with PICI Investigator Aram Lyu, PhD, (UCSF) serving as first author—and including PICI Investigators Zenghua Fan, PhD, Kai Wu, MD, PhD, (UCSF) and Eliezer Van Allen, MD (Dana-Farber Cancer Institute)—has uncovered a key mechanism behind this long-standing challenge. Their PICI-funded study in Nature reveals how prostate cancer evades immune attack—and, importantly, identifies a promising strategy to overcome this resistance. The team's research illuminates:  → A distinct immune cell population (SPP1hi-TAMs) that becomes increasingly prevalent as prostate cancer progresses, creating a previously unrecognized barrier to immune response → The role of adenosine signaling as a key mediator of immune suppression, specifically targetable with the selective inhibitor ciforadenant → Clinical evidence that disrupting this pathway in combination with the immune checkpoint inhibitor drug atezolizumab can induce meaningful responses in select patients with advanced disease Why it matters: For the approximately 290,000 Americans diagnosed with prostate cancer each year, immunotherapy has remained largely out of reach. This discovery not only explains why but also reveals specific cellular targets and pathways to pursue. By identifying both a mechanism of resistance and a potential strategy to overcome it—along with markers to pinpoint which patients might benefit most—this work opens new possibilities for treatment where few options currently exist. → Read more in Nature: https://lnkd.in/g63ieA-k

A team of researchers at the University of Pennsylvania, led by PICI Investigator Joseph Fraietta, PhD, and including E. John Wherry, PhD, Co-Director of the PICI Center at Penn and 2022 Parker Bridge Fellow Evan Weber, PhD, has made a breakthrough in understanding and overcoming T cell exhaustion—one of the biggest challenges in #cancerimmunotherapy and chronic infection control. In a PICI-funded study recently published in Science Advances, the team uncovered how TET2, a critical regulator, drives T cells toward exhaustion during chronic viral infection. Building on this insight, they engineered CAR T cells with significant advancements: → Enhanced durability: By targeting TET2, the team developed CAR T cells that remained active longer, demonstrating superior antitumor responses in preclinical models. → Improved safety: A built-in "safety switch" allows for the controlled depletion of TET2-targeted cells if needed, reducing the potential risk of adverse effects. → Expanded potential: This approach offers promise in addressing major barriers in treating solid tumors, where traditional CAR T therapies have struggled. Why it matters: This research fundamentally redefines how we can engineer CAR T cells, opening new therapeutic possibilities for cancers that have long resisted current immunotherapy approaches. Congratulations to the team on this milestone achievement! → Read the study: https://lnkd.in/dKmA53Yt

PICI is thrilled to announce the 2024 Representation in SciencE (RISE) Scholars, a group of seven exceptional researchers selected through our Diversity, Equity, Inclusion and Belonging (DEIB) Program. Thanks to the generosity of an anonymous donor who shares our vision for a world where all cancers are curable, we’re proud to directly invest in these scholars as they drive new advancements in cancer immunotherapy. Meet the 2024 RISE Scholars:  → Sofía Castelli, PhD Candidate, University of Pennsylvania  → Maggie Colton Cove, PhD Candidate, University of California, San Francisco → Javier Glez-Vaz, PhD, UCLA → Rosmely Hernandez, PhD, Gladstone Institutes  → Jee Hye Kang, PhD Candidate, Weill Cornell Medicine  → Corey Perkins, PhD, Dana-Farber Cancer Institute,  → Grayson Rodriguez, PhD, Stanford University School of Medicine Each scholar will receive $75,000 to drive their innovative research, totaling $525,000 funded by our generous donor. Their projects target critical challenges in immunotherapy, including: enhancing CAR T-cell treatments for solid tumors, novel approaches to overcoming immunotherapy resistance, advancing T cell engineering and understanding tumor microenvironments. We are honored to champion these brilliant minds as they pursue breakthroughs in cancer treatment. Don't just imagine a world where all cancers are curable—help make it a reality. Your support empowers innovators like our RISE Scholars to transform cancer care. Contribute now at www.parkerici.org/donate. → Congratulations to the 2024 RISE Scholars! Read our latest blog post to learn more: https://lnkd.in/exsrsPPP #CancerResearch #Immunotherapy

PICI Chief Scientific Officer John Connolly, PhD, joined Brad Loncar of BiotechTV to discuss the latest immunotherapy trends at Society for Immunotherapy of Cancer (SITC)’s Annual Meeting last weekend. He shares his excitement around the latest immuno-oncology developments and areas to watch in cancer research, including: → Advances in biologics and the rising importance of AI and machine learning → Cutting-edge research in cell therapy, including innovations in solid tumors with TIL therapies, as well as a CAR T that secretes a bispecific, a significant advance now being studied in the clinic and led by PICI Collaborator Marcela Maus, MD, PhD, Massachusetts General Hospital → Progress driven by PICI portfolio companies Check out the full interview to hear more from Dr. Connolly at #SITC24: https://lnkd.in/ggbtwshp For more on PICI’s extensive presence at the meeting, take a look back at our blog: https://lnkd.in/esGb875h

Can immune cells be engineered to fight cancer with greater precision? Researchers led by Kole Roybal, PhD, Director of the PICI Center at University of California, San Francisco, have developed SNIPR (synthetic intramembrane proteolysis receptor), which enables T cells to detect soluble tumor signals and activate selectively within tumors. Published in Nature Magazine, this breakthrough addresses a key challenge in cell therapy: achieving precise tumor targeting while minimizing harm to healthy tissues. The team collaborated with Nobel laureate David Baker, PhD, Professor of Biochemistry and Director of The Institute of Protein Design at the University of Washington - School of Medicine, and Co-Founder of PICI portfolio company Xaira Therapeutics. Key insights: → Tumor-specific activation: SNIPRs detect soluble factors like TGF-β and VEGF, activating T cells only within the tumor microenvironment, sparing healthy tissues. → Improved safety & efficacy: In preclinical models, SNIPR-equipped T cells demonstrated strong anti-tumor effects with reduced toxicity, thanks to their pH-dependent activation mechanism. → Programmable cell communication: SNIPRs create synthetic signaling networks, enabling engineered cells to communicate and coordinate more effectively, paving the way for advanced multi-cellular therapies. Impact for patients: SNIPR technology could expand CAR T-cell therapies by allowing T cells to target tumor environments more precisely, offering safer and more effective treatments—especially for solid tumors, where off-tumor toxicity has been a significant hurdle. Looking ahead: SNIPRs represent a major leap forward in synthetic biology, with potential applications beyond cancer immunotherapy. These receptors could play a role in regenerative medicine, autoimmune disease treatments and advanced diagnostics. → Read more in Nature: https://lnkd.in/g9WNmANs → View the article from UCSF: https://lnkd.in/gtZ5Gmze

Nature Magazine has just published pivotal findings on GD2-CAR T-cell therapy for childhood brain cancer – a novel therapy that recently received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA. This PICI co-funded study demonstrates significant potential in addressing pediatric diffuse midline gliomas (DMG), a devastating cancer with few treatment options. What distinguishes this therapy is its dual impact: reducing tumor size while also restoring lost neurological functions – an advancement in treating these aggressive tumors. Key findings include: → Neurological recovery: 9 out of 11 treated patients experienced substantial improvements in neurological function. → Tumor reduction: Tumor size was reduced by more than 50% in four patients. → Noteworthy outcome: One patient achieved a complete response, remaining healthy for four years post-diagnosis. Led by Crystal Mackall, MD, Director of the PICI Center at Stanford University School of Medicine, and PICI Project Member Michelle Monje, MD, PhD, this study exemplifies the impact of strategic collaboration in advancing new therapies. The RMAT designation fast-tracks the pathway to potential approval, accelerating access to this promising treatment. For more details on the RMAT designation, check out the post below. Explore the full findings: Nature article: https://lnkd.in/gytvRfjY Stanford Medicine feature article: https://lnkd.in/g9gCdqVv #FDA #Pediatric #Cancer