Parker Institute for Cancer Immunotherapy

PICI applauds the FDA's decision to grant Regenerative Medicine Advanced Therapy (RMAT) designation to the GD2-CAR T-cell therapy for diffuse midline gliomas (DMG), developed by Crystal Mackall, MD, Director of the PICI Center at Stanford University School of Medicine, and Michelle Monje, MD, PhD, and team. DMGs are devastating and almost always fatal pediatric cancers, with no approved therapies beyond palliative care. This FDA decision expedites the development and review of this innovative treatment. The PICI-co-funded, first-in-child trial, in collaboration with Stanford, California Institute for Regenerative Medicine (CIRM) and CureSearch for Children's Cancer, was conducted at Stanford Children's Health | Lucile Packard Children's Hospital Stanford, with Dr. Monje serving as the study's principal investigator and by the Center for Cancer Cell Therapy at Stanford, led by Dr. Mackall. Early results have been remarkable, showing improved neurological function, tumor shrinkage, and even a complete, durable response lasting over three years in one child. Results from Arm A of this study will be published in the coming weeks. The RMAT designation represents a critical step forward, as it enables more direct collaboration with the FDA throughout the approval process. This aligns with PICI’s commitment to breaking down barriers and accelerating patient access to life-saving treatments through collaboration and innovation. We extend our congratulations and gratitude to Drs. Mackall and Monje and team for their relentless dedication to finding cures for these devastating childhood cancers. #FDA #Pediatric #Cancer

The impact of brilliant scientific minds can change the course of medicine forever. Join us in congratulating E. John Wherry, PhD, Co-Director of the PICI Center at the University of Pennsylvania, and PICI Investigator Nina Bhardwaj, MD, PhD, Icahn School of Medicine at Mount Sinai, on their election to the National Academy of Medicine. Behind this prestigious honor lies years of dedication to understanding cancer's complexities. Dr. Wherry's work on T cell exhaustion and Dr. Bhardwaj's research in dendritic cell biology are advancing our understanding of cancer treatment and improving patient care. Their election to the Academy recognizes not only their scientific achievements but also their lasting influence on the field of cancer immunotherapy. As valued members of the PICI Network, they continue to collaboratively drive progress toward our shared mission of turning all cancers into curable diseases. Thank you, Drs. Bhardwaj and Wherry! Learn more: https://lnkd.in/gXfSqCT9 #CancerImmunotherapy #PICIPioneers

Researchers from the Dana-Farber Cancer Institute have engineered E. coli bacteria to function as a targeted delivery system for cancer-fighting therapies, effectively creating a "tumor GPS." This unconventional approach, published in Nature Biotechnology, has the potential to transform the treatment of solid tumors. The team was led by PICI Investigator Rizwan Romee, MD, and included PICI Investigators Catherine Wu, MD, and David Barbie, MD. In preclinical mouse studies, the engineered E. coli demonstrated: → Precise targeting: The bacteria successfully delivered immune-activating cytokines directly to tumor cells, enhancing the efficacy of CAR-NK cell therapy. → Potent antitumor activity: In mouse models, this approach resulted in 50-60% cure rates and showed superior antitumor effects compared to immune checkpoint inhibitor therapy. → Promising efficacy in challenging cases: The therapy safely and effectively induced strong antitumor responses in treatment-resistant solid tumors, including mesothelioma. By leveraging the natural tumor-seeking properties of gut bacteria, this novel technique could significantly improve the delivery and efficacy of cancer immunotherapies. Kudos to the team for enlisting biology’s most unexpected allies in the fight against cancer—true scientific ingenuity! Read more in Nature Biotechnology: https://lnkd.in/dXAGtWdy Learn more from Dana-Farber:  https://lnkd.in/eYuwUZeX #NKCells  #TumorMicroenvironment

PICI is proud to continue our collaboration with UCLA Health and the UCLA Health Jonsson Comprehensive Cancer Center, a founding member of the PICI Network. Under the leadership of Drs. Antoni Ribas and Owen Witte, the team of distinguished PICI Investigators at UCLA is advancing innovative cell therapies and conducting pioneering clinical trials with the potential to transform #cancertreatment. Our collaboration has already delivered breakthroughs in CAR T-cell therapies, including a dual-target trial for B-cell lymphomas, and is pushing the boundaries of research into solid tumors. We look forward to their continued success as part of the PICI Network! Thank you to all those at UCLA who have contributed to the PICI mission and PICI Center, including Member Researchers such as: Katie Campbell, PhD, Yvonne Chen, PhD, Gay Crooks, MD, Francisco Javier Gonzalez Vaz, PhD, John K. Lee, MD, PhD, Robert Prins, PhD, Cristina Puig Saus, PhD, Caius Radu, MD, Gabriel Abril Rodriguez, PhD, Chris Seet, MD, PhD, and Lili Yang, PhD.

PICI congratulates Sean Yamada-Hunter, PhD, a Parker Scholar at Stanford University School of Medicine, for being named a 2024 STAT Wunderkind! This prestigious award recognizes the next generation of scientific superstars who are advancing the frontiers of medicine and technology. Dr. Yamada-Hunter's research at the PICI Center at Stanford Medicine focuses on developing novel immunotherapies that harness the power of the body's own immune system to fight cancer. In collaboration with Crystal Mackall, MD, Director of the PICI Center at Stanford Medicine, he is engineering CD47 to enhance the cancer-killing abilities of T cells and macrophages. As a 2024 PICI Early Career Researcher and a valued member of the PICI Network, Dr. Yamada-Hunter embodies the dedication to scientific excellence and innovation that drives PICI's mission to turn all cancers into curable diseases. His commitment to translating these promising therapies from the lab to the clinic underscores the potential for significant and lasting impact on human health. Read more from STAT: https://lnkd.in/gEzDVT27 Learn more about Sean’s Early Career Researcher award from PICI: https://lnkd.in/eMEsdCbF

Glioblastoma (GBM) remains one of the most difficult cancers to treat, in part due to its immunosuppressive tumor microenvironment. A key player in this suppression is TGF-β, a molecule that acts as a shield, protecting the tumor from immune attack. Now, a team led by PICI Investigator  Yvonne Chen, PhD, UCLA, including PICI Investigators Hideho Okada, MD, PhD, University of California, San Francisco, Robert Prins, PhD, UCLA, and Christine Brown, PhD, City of Hope has engineered a breakthrough CAR T-cell therapy that not only targets GBM cells but also reprograms the tumor microenvironment by converting TGF-β from a suppressor into an immune activator. Published in OUP Academic’s Neuro-Oncology journal (Society for Neuro-Oncology), this research unveils a "Trojan horse" strategy to overcome GBM's defenses. Here's how it works: → TGF-β Reprogramming: The bispecific CAR T cells convert TGF-β from an immune suppressor into an activator, turning the tumor’s defenses against itself. → Improved T-cell Infiltration: These engineered CAR T cells penetrate the tumor more effectively than conventional therapies, breaking through barriers that typically prevent immune cells from reaching the cancer. → Enhanced Survival: Preclinical models have shown significantly extended survival, offering hope in the fight against this aggressive disease. This technique – engineering multifunctional CAR T cells that can both target cancer and modulate the tumor microenvironment – represents a significant advancement that could potentially be applied to various solid tumors. Congratulations to the team on this breakthrough! Read more in Neuro-Oncology: https://lnkd.in/ejdHgNw3 #CARTCellTherapy #SolidTumorImmunotherapy

Imagine giving your immune system’s cancer-fighting cells a powerful energy boost to take on tumors. That’s exactly what researchers at Stanford University School of Medicine have achieved. Led by Crystal Mackall, MD, Director of the PICI Center at Stanford Medicine, their new study published in Nature Communications reveals how increasing glucose uptake in CAR T cells can enhance cancer immunotherapy, improving CAR T cell function and antitumor potency. By overexpressing GLUT1, a glucose uptake protein, the team effectively reprogrammed CAR T cells, providing them with a crucial metabolic advantage. This reprogramming led to: → Enhanced metabolic capacity: Increased glucose uptake fuels both glycolysis and oxidative phosphorylation, giving CAR T cells more energy for anti-tumor activity. → Increased persistence: GLUT1 overexpression reduces T cell exhaustion, allowing engineered cells to maintain their killing capacity longer within tumors. → Optimized T cell differentiation: The metabolic shift promotes differentiation of Th17 cells, a T cell subset that showed enhanced anti-tumor activity in this study. → Enhanced resilience: Improved metabolic pathways boost CART cells' resistance to oxidative stress in the tumor microenvironment. These findings highlight the critical role of metabolism in immune function and offer a novel way to engineer more potent, persistent CAR T cells using a naturally occurring glucose transporter. This opens new avenues for optimizing cell therapies and could pave the way for more effective cancer treatments. Congratulations to Dr. Mackall and team! Read the full study: https://lnkd.in/eaYYUvJw #CARTCellTherapy #TumorMicroenvironment

PICI is honored to congratulate David Baker, PhD, co-founder of PICI portfolio company Xaira Therapeutics, on receiving the 2024 Nobel Prize in Chemistry for his pioneering work in computational protein design.  Dr. Baker, professor of biochemistry at the University of Washington - School of Medicine and director of the Institute for Protein Design, University of Washington, has made phenomenal contributions at the forefront of drug discovery and artificial intelligence, holding immense promise for societal impact. By developing AI-powered tools that analyze existing proteins and design novel ones, he has achieved a tremendous breakthrough in the field. We are proud to count Dr. Baker a friend and fierce collaborator of the PICI Network. It has been a privilege to learn from him in various capacities, including as a speaker at our PICI Scientific Retreats. His relentless pursuit of bold ideas continues to shape the future of biotech research. Read more: https://lnkd.in/exQYFfAf

Congrats to 2024 Parker Scholar Debolina Ganguly, PhD, from Dana-Farber Cancer Institute! Dr. Ganguly’s innovative work on metastatic cancer cells and immune response is truly impressive and holds promise for shaping new, effective cancer treatments. We’re proud to support her collaborations with PICI Investigator Judith Agudo, PhD, and Elizabeth Mittendorf MD, PhD, Co-Director of the PICI Center at Dana-Farber, highlighting how mentorship and teamwork propel cancer immunotherapy. PICI's Early Career Researcher program, with over $1 million invested in 2024 and $22.5 million since 2016, provides emerging investigators with critical support and mentorship to pursue bold ideas and fuel innovation, shaping the future of immunotherapy. Join us in celebrating Dr. Ganguly and her fellow 2024 awardees!

Our newest Immuno-Oncology Digest is here! The October edition features news from across the PICI Network, industry updates, breakthrough #immunotherapy publications and more. Check out: → Commentary on former President Jimmy Carter’s treatment for metastatic melanoma and the efficacy of immunotherapy for patients at various stages of life from F. Stephen Hodi, MD, Co-Director of the PICI Center at Dana-Farber Cancer Institute, Antoni Ribas, MD, PhD, Director of the PICI Center at UCLA and Jedd Wolchok, MD, PhD, Director of the PICI Center at Weill Cornell Medicine. →A glimpse of our Fall Scientific Retreat, where the PICI Network came together to connect, exchange ideas and collaborate on translating cutting-edge science into cancer treatment outcomes! → A decade of follow-up from the landmark CheckMate 067 trial, underscoring immunotherapy’s impact on advanced #melanoma treatment with key contributions from researchers including Drs. Jedd Wolchok, and F. Stephen Hodi. → Multiple new immunotherapy publications from PICI Investigators, including Mohammad Rashidian, PhD, Dana-Farber Cancer Institute, Hideho Okada, MD, PhD, Taha Merghoub, PhD, Co-Director of the PICI Center at Weill Cornell Medicine, Carl June, MD, Director of the PICI Center at the University of Pennsylvania, Bhardwaj Nina, MD, PhD, Icahn School of Medicine at Mount Sinai, Lewis Lanier, PhD, University of California, San Francisco, and more! Read the full digest, with all the latest news: https://lnkd.in/ejAZFyrc Subscribe to stay updated on everything PICI: https://lnkd.in/g2hVZQub