In this month’s ACGT Research News Roundup, we’re covering new publications in cell and gene therapy research, exciting developments in the clinic and biotech, and highlighting research from our ACGT Scientific Advisory Council (SAC) and Research Fellows.
Cancer Cell and Gene Therapy Industry News
T cell researchers receive the Nobel Prize in Physiology or Medicine
Three immunology researchers, Mary Brunkow, PhD (Institute for Systems Biology), Fred Ramsdell, PhD (Sonoma Biotherapeutics) and Shimon Sakaguchi, MD, PhD (Osaka University), received the Nobel Prize in Physiology or Medicine for their historic discoveries on the role of regulatory T cells in the function of the human immune system and how they prevent the human immune system from turning against itself.
Their research has provided some of the bedrock upon which more modern immunology has been built, and has made further insights into the use of T cells to fight cancer possible. Their enlightening lecture on their discoveries is available for viewing on YouTube.
Link Industries launches to create next-gen CAR-T therapies
The biotechnology company Link Industries announced on December 15 that[Office2] it is officially launching with a mission to create next-generation CAR-T therapies for cancer, touting $60 million in series A financing led by Johnson & Johnson’s venture capital organization, among other big-name investors.
Link Industries was founded in 2022 out of Stanford University, with founders that include ACGT SAC member Crystal Mackall, MD. Their lead program is in preclinical development for renal cell carcinoma, and another program for colorectal cancer is set to begin in-human testing in 2027.
Rockefeller researchers reveal new findings on TCR function
Researchers from The Rockefeller University published findings revealing new key findings on the function of T-cell receptors (TCR), providing a deeper understanding on how the TCR signaling system works that could allow for refinement and expansion of T cell therapies for new types of cancer.
Their research used a lipid mixture that replicated a TCR’s in vivo environment, which, when removed with detergent, showed that TCRs activate when encountered with an antigen or suspect particle, discoveries that ran counter to previous cryogenic electron microscopy analyses.
Vyriad unveils new in vivo CAR-T candidate
The biotechnology company presented data on its lead in vivo CAR T therapy candidate, VV169, at the American Society of Hematology (ASH) Annual Meeting, showing 100% clearance of disseminated myeloma tumors in mice within 28 days.
Led by CEO and ACGT SAC member Stephen J. Russell, MD, Vyriad also presented promising data on lentiviral vector retargeting strategies across three in vivo approaches. Vyriad plans to begin a clinical trial in the United States this year.
Base-edited gene therapy shows results against T-ALL
A team of researchers at Great Ormond Street Hospital published results in the New England Journal of Medicine showing that their base-edited CAR therapy, BE-CAR7, has been used to treat a previously untreatable form of blood cancer, T-cell acute lymphoblastic leukemia.
Starting in 2022, 11 people, including nine children, have undergone the treatment as part of a clinical trial that has resulted in 82% going into deep remission and 64% now presenting as disease-free, with only manageable and tolerable side effects.
Cancer Cell and Gene Therapy Research Highlights from ACGT’s SAC and Research Fellows:
Clinical Cancer Research: Pancreatic Cancer Organoids Recapitulate Chemotherapy Response and Identify a Potent Cytotoxic T-Cell Population.
A team of researchers, including ACGT SAC Chair Michael T. Lotze, MD (University of Pittsburgh), published results from a study using tumor-infiltrating lymphocytes (TILs) and patient-derived organoids (PDOs) to predict the individual components of potentially successful combination therapies for pancreatic ductal adenocarcinoma.
Blood: Long-term Follow-up of Gastrointestinal CAR T-cell Lymphoma: Homing, Clonal Expansion, and Response to Cyclosporine.
ACGT SAC member Crystal Mackall, MD (Stanford University), was co-author of a study that investigated the mechanisms underlying CAR T-cell-associated lymphomagenesis in a lymphoma patient, producing insights on the patient’s response to cyclosporine and how CAR T-cell therapy interacts with the tumor microenvironment.
Journal for Immunotherapy of Cancer: A phase I clinical trial of intravesical therapy with autologous tumor-infiltrating lymphocytes (TIL) in BCG-exposed non-muscle invasive bladder cancer.
Researchers, including ACGT SAC member Shari Pilon-Thomas, PhD (Moffitt Cancer Center), published results from a Phase I trial of an intravesical TIL therapy for nine patients with high-risk non-muscle invasive bladder cancer, producing positive results that “support the feasibility of this approach.”
Cancer Cell and Gene Therapy Research Publications from ACGT’s SAC and Research Fellows:
Journal of Clinical Investigation: Fanning the flames: IFN-γ fuels CAR-T inflammation and cytopenia. Marcela V. Maus, MD, PhD (Massachusetts General Hospital).
Science Advances: HLA-Shuttle: A system for enhancing antigen presentation in immunologically cold tumors. John Maris, MD (Children’s Hospital of Philadelphia).
Leukemia: Prognostic value of serological and PET/CT response kinetics in patients with multiple myeloma treated with BCMA CAR-T. Marcela V. Maus, MD, PhD (Massachusetts General Hospital).
Blood Advances: Ibrutinib exposure correlates with improved efficacy of CAR T-cells in patients with mantle cell lymphoma. Marcela V. Maus, MD, PhD (Massachusetts General Hospital).
Blood: CAR T cells targeting C-C motif chemokine receptor 4 (CCR4) selectively deplete human Tregs ex vivo and in vivo. Carl H. June, MD (University of Pennsylvania).
Cell: pTα enhances mRNA translation and potentiates CAR T cells for solid tumor eradication. Michel Sadelain, MD, PhD (Columbia University).
Nature Biomedical Engineering: mRNA engineering of allogeneic mesenchymal stem cells enables coordinated delivery of T cell engagers and immunotherapeutic cues. Christopher Jewell, PhD (University of Maryland).
