Session Details

Plenary Session 3 - Redirecting Immune Cells - T and NK cells aside from canonical CARs
Saturday, September 14, 2019 08:45 AM - 10:15 AM
Plenary Hall
The show-stopping initial efficacy of CAR T cells revolutionized the field of cancer antigen-targeted immunotherapy, but optimizing efficiency and safety especially in the setting of solid tumors and myeloid malignancies, for example, may require exploiting other cell therapy approaches.  These include expansion of antigen-specific T cells without genetic engineering (CTLs or TILs), alternative genetic targeting approaches (eTCR and TACs), capitalizing on NK-cell recognition of malignant transformation, or modulation of the tumor microenvironment.  Cell therapy is even making inroads now in to autoimmune diseases and modulation of the inflammatory milieu.  In this session, we will highlight the translation of T and NK cell therapies other than canonical CARs to clinical use.

Chair:

Sarah Nikiforow, MD, PhD Dana-Farber Cancer Institute, USA

Speakers:

T cell approaches to fight infections and leukemia without causing graft-versus-host disease
Denis-Claude, MD, FRCPC, Hopital Maisonneuve-Rosemont, Canada
T-cell mediated cellular immunotherapy is clearly one of the most exciting breakthroughs of this century. Several methods for ex vivo selection, manipulation and expansion of T cells enables focused elimination of infectious agents and leukemia cells. We will discuss different strategies that take advantage of T cells specificity and potency to overcome these complications. In the context of haplo-identical stem cell transplantation, it is now possible to treat donor T cells ex vivo in order to remove anti-host reacting T cells in order to prevent graft-versus-host disease, while preserving anti-infection and anti-leukemia T cells. This strategy is eliminating the need for post-transplant prophylaxis with immunosuppressive agents. This approach is currently being evaluated in an international randomized Phase III clinical trial. We have also developed an approach to specifically target antigenic polymorphisms in the form of minor histocompatibility antigens that are preferentially expressed on patient leukemia cells. T cells can also be used for immune tolerance induction, either in the context of graft-versus-host disease or organ rejection. Several approaches using regulatory T cells will also be discussed
Off-the-shelf Natural Killer cell-based therapies for malignancies
Sumithira Vasu, MBBS, Comprehensive Cancer Center, Ohio State University, USA
Natural Killer (NK) cells are a key component of anti-tumor immunity which, unlike T cells, recognize cancer in a manner that ignores self, is not antigen-specific nor major histocompatibility complex (MHC)-restricted, and induces a pro-inflammatory environment that primes adaptive immunity. NK cell numbers and function are low in a wide variety of malignancies, traffic poorly to tumor sites or across the blood-brain barrier, and are further depleted by chemotherapy, radiation, and surgical anesthesia. This provides a strong rationale for restoring NK cell function through adoptive transfer, which overcomes the problems of low numbers by generating large number of highly active NK cells from donor or patient peripheral blood, using feeder cells expressing IL-21. Over 200 infusions of expanded NK cells have been administered to over 80 subjects (including pediatric patients with leukemia, brain tumors, and neuroblastoma) in ongoing trials, demonstrating safety and efficacy. However, broad application of NK cell adoptive transfer has been hindered by the high cost and delay involved in manufacturing individualized cell therapeutic products. To address this, we have developed an off-the shelf, third-party approach that establishes a process and infrastructure to identify donors to generate pre-made banks of ready-to-infuse NK cells.

Genetic Engineering Cells for Solid Tumors
Lisa Butterfiled, PhD Parker Institute for Cancer Immunotherapy; UCSF, USA
The solid tumor microenvironment is a hostile environment for effector cells. Analysis of NK cells and T cells infiltrating tumors has identified several areas for intervention to improve trafficking, infiltration and activity of effectors in patients. Clinical trial data of antigen-specific T cell activity, NK activation and new strategies for altering effectors will be presented.