15 sessions focus on breaking developments in cancer research; T cell exhaustion and CAR-T cell manufacture and delivery were two of the important topics discussed
Friday’s opening day of the American Association for Cancer Research (AACR) Annual Meeting 2024 featured 11 education sessions and 4 methods workshops in advance of the full-scale meeting starting on Saturday morning April 6, and running through Wednesday afternoon, April 10. The AACR has over 58,000 members in 141 countries and territories, and this year’s meeting in San Diego, California, has recorded 23,000 registrants (in-person attendees as well as many virtual attendees). Attendees will be rewarded with great networking opportunities and an incredibly rich program of presentations, industry exhibits, clinical trial reports, and research posters documenting recent progress in the accelerating field of cancer research. We will highlight two of Friday’s 15 sessions below.
Exhausted T Cells
One of the Friday’s education sessions focused on the “Determinants and Meanings of T Cell Recognition, Exhaustion, and Persistence.” The introduction to this session said the following:
“Understanding of the factors that connect antigen-specific T cell recognition to T cell phenotype and long-term in vivo persistence constitutes foundational knowledge for understanding and designing cancer immunotherapy strategies that can be harnessed to more effectively treat broad classes of solid tumors. A particular case in point is that of the exhausted T cell phenotype. The use of the term ‘exhausted’ emerged out of work on chronic viral infections, and observations that certain T cells exhibited diminished effector functions following extended antigen stimulation.”
“It is now recognized that ‘exhausted’ T cells actually comprise multiple phenotypes that reside across a diverse epigenetic landscape – a subset of which can be reactivated to exhibit potent anti-tumor functions. Other factors relevant to the engineering of successful cancer immunotherapy treatments, such as the biological properties of T cells that will persist through a disease course, relative to those that will likely be transient, are also becoming better resolved.”
“This increase in understanding has been fueled by several developments in the field. One development has been the emergence of data sets that provide quantitative measurements, in the same single T cells, of T cell phenotype, TCRa/ß genes, and Class I and Class II antigen specificity, across patient populations and in multiple disease settings. Such data sets have, in turn, provided input into computational and genetic models that can parse through the resulting high-dimensional space to identify biological, biochemical, and biophysical factors that influence the three T cell axes of recognition, phenotype, and persistence.”
“Other ongoing developments have been the elucidation of the T cell epigenetic programs that encode specific T cell phenotypes (and sub-phenotypes), and the factors like metabolism and neural controls that can favor one phenotype over another. In this focused AACR tutorial, the presenters will speak to these various scientific and technological advances, and discuss how they might be harnessed, in the near future, to improve cancer immunotherapy effectiveness in challenging tumor settings.”
This session was chaired by James Heath, PhD, President and Professor of the Institute of Systems Biology, and featured the following presentations:
“T Cell Exhaustion and Relevance in Cancer Immunology” by E. John Wherry, PhD, Chair of the Department of Systems Pharmacology & Translational Therapeutics, Director of the Institute for Immunology, University of Pennsylvania.
“Are Tumor-Reactive CD8 TIL Exhausted or Can They Be Rescued for Clinical Benefit?” by Andrew Weinberg, PhD, Chair of Laboratory of Basic Immunology, Earle A. Chiles Research Institute, Providence Cancer Institute.
“Predicting the T Cell Characteristics of Recognition, Exhaustion, and Persistence: Limitations and Opportunities” by Dr. Heath.
“Metabolic and Neural Regulation of Immunity and Cancer” by Tak Mak, PhD, Princess Margaret Cancer Centre. Dr. Mak first became widely known for his discovery of the T-cell receptor in 1983 and pioneering work in the genetics of immunology. In 1995, Mak published a landmark paper on the discovery of the function of the immune checkpoint protein CTLA-4, thus opening the path for immunotherapy/checkpoint inhibitors as a means of cancer treatment.
CAR-T Cells: Manufacturing and Delivery
One of the following sessions focused on “Implementing Alternative Manufacturing and Delivery Models to Improve Access to CAR-T Therapy.” The introduction to this session is given below.
“CAR-T therapies are effective for blood cancers, but patient access remains limited in most jurisdictions. This is due to many factors including the complexity and cost of manufacturing & distributing these extensively regulated autologous cell products, the need for specialized in-patient care, complex reimbursement models, and the dense intellectual property landscape. Alternative manufacturing & delivery models, for example the “Point of Care” model, where CAR-T products are prepared locally in the hospital setting, present unique challenges but also potential benefits, including the potential for increased patient access. This model is being successfully implemented in several different countries.”
“The objectives of this session will be for invited speakers to discuss barriers to CAR-T access and/or relate their experiences along non-conventional paths from CAR-T pre-clinical development and manufacturing set-up, to early-stage clinical trials and eventual regulatory approval. The session will provide the opportunity for increased collaboration among investigators active in this area and provide useful information for others considering alternative models.”
The session was chaired by Robert Holt, PhD, who is currently a Distinguished Scientist at the BC Cancer Research Centre, where he is also Co-Director of the BC Cancer Immunotherapy Program (in Vancouver, Canada). He is also appointed as Professor of Medical Genetics at the University of British Columbia and Professor of Molecular Biology & Biochemistry at Simon Fraser University.
The other speakers were as follows:
Rayne Rouce, MD, Associate Professor, Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine; Associate Director, Community Engagement, Office of Diversity, Baylor College of Medicine.
“The CLIC Point-of-Care Manufacturing Platform for CAR-T Clinical Trials in Canada” by Natasha Kekre, MD, Associate Professor, Department of Medicine, University of Ottawa; Staff Hematologist, Blood and Marrow Transplant Program, Ottawa Hospital – General Campus; Associate Scientist, Ottawa Hospital Research Institute.
“A Non-Profit Approach to Cell and Gene Therapy: Lowering Costs to Advance Equity” by Rimas Orentas, PhD, Professor, Pediatrics Division of Hematology Oncology, Bone Marrow Transplant, University of Washington.
by Michael D. O’Neill