Immunotherapy: Activating Your Immune System to Fight Disease
*This is a draft agenda and is subject to change.
SUNDAY, AUGUST 25, 2019
Kansas City Convention Center
301 W 13th St. 2100 Entrance, Room 2103 A
Kansas City, MO
WELCOME AND INTRODUCTIONS
Dennis Ridenour, BioNexus KC
Klaus Hellmann, KLIFOVET AG
Autologous Activated T cell Therapy for Osteosarcoma of Companion Dogs
Canine osteosarcoma (OSA) is an aggressively metastatic primary bone malignancy with frequent chemotherapy failure. We hypothesized that dogs with OSA would be safely treated with autologous vaccination, adoptive T cell transfer (ACT) of ex vivo-activated T cells and low dose human interleukin-2 (IL-2) resulting in improved survival compared to carboplatin.
Jeffrey Bryan, DVM, PhD, University of Missouri
(Dr. Bryan will be presenting his research in conjunction with Elias Animal Health technology)
Mary Lynn Higginbotham, Kansas State University
Experimental Autologous Cancer Vaccine
Ashley Kalinauskas, Torigen Pharmaceuticals
Novel Therapeutic Bovine Ultralong Antibodies
Innovative solutions are required to address some of the most challenging human and animal diseases for which traditional methods have failed to produce effective countermeasures. A neutralizing B-cell epitope is the fundamental unit targeted by a neutralizing antibody to confer protection. However, some pathogens, such as Human Immunodeficiency Virus [HIV] and Porcine Reproductive and Respiratory Disease Syndrome [PRRSV], have a high mutation rate, such that the virus can escape antibody recognition. However, some rare epitopes are required for crucial function, and are thus not easily mutable. These epitopes are highly conserved among disparate strains and thus, they are targets for generating cross-protective neutralizing antibodies. These epitopes are often hidden, masked, or only exposed when needed. Identification of such epitopes is critical if prophylactics/therapeutic approaches to these challenging viruses are to succeed. We have found that the cow antibody repertoire has evolved unique structural and genetic features that may help us identify and understand neutralizing epitopes on viruses. Notably, we have demonstrated that immunization of cows with well-ordered HIV gp120 antigen or whole PRRS virus elicited potent broadly neutralizing antibodies. Overall, this approach will enable mapping of clinically relevant pathogen epitopes for development of contemporary prophylactics and or therapeutics.
Waithaka Mwangi, Kansas State University
Chris Lorson, University of Missouri
MONDAY, AUGUST 26, 2019
WELCOME AND INTRODUCTIONS
Mark Nichols, PhD University of Missouri – Kansas City
Harnessing Natural and Engineered Properties of NKT cells for Adoptive Cancer Immunotherapy
NKT cells are attractive carriers of chimeric antigen receptors (CAR) due to their inherent antitumor properties and preferential localization to tumor sites. Unlike conventional T cells, NKT cells are non-alloreactive and could be used as off-the-shelf therapies without the risk for graft-versus-host disease. However, low frequency of NKT cells in human peripheral blood presents a fundamental challenge for clinical development of NKT cell-based therapeutics. To address this limitation, we have developed the current good manufacturing practice (cGMP) protocol for rapid generation of large numbers of NKT and CAR-NKT cells from leukapheresis products. This technology has enabled the initiation of first-in-human CAR-NKT clinical trial in children with neuroblastoma.
Leonid Metelitsa, Texas Children’s Hospital
Debra Webster, Cardinal Health
Joseph McGuirk, University of Kansas Medical Center
Joshua Sestak, Orion Biosciences
NextGen Now – The Future of ATMP Facilities
ATMP processes have fallen back on manual operations to accommodate the patient specific scale, but what will these facilities look like in five years? The race for process closure and automated solutions has already begun. Don’t miss out as CRB discusses what will drive the industry to reduced operating costs, more efficient staff utilization and improved reliability and product reproducibility.
Doug Myers, MD, Children’s Mercy
Immune Profiling Reveals Antigen Spreading after HER2 CAR T-cell Therapy in Sarcoma
Chimeric Antigen Receptor (CAR) T cells combine the specificity of an antibody with the functionality of T cells. A phase I study testing CAR T cells targeting human epidermal growth factor receptor 2 (HER2) is currently ongoing for patients with advanced HER2 positive sarcoma (NCT00902044). In this trial, multiple infusions of HER2 CAR T-cells in a child with refractory alveolar rhabdomyosarcoma (RMS) metastatic to the bone marrow, induced a complete response (CR) that was durable. The objective clinical benefit observed in the patient was investigated to identify involvement of broader host immune responses that may have contributed to tumor elimination. Following the CAR T-cell infusion, we observed remodeling of the T-cell receptor (TCR) repertoire in the peripheral blood and bone marrow metastatic sites. Additionally, evaluation of the CAR T-cell induced endogenous humoral immune response identified autoantibody generation against proteins involved in oncogenic signaling pathways in rhabdomyosarcoma.
Sujith Joseph, PhD, Baylor College of Medicine
Discovery of Anti-PD-L1 Peptides for Cancer Immunotherapy
Immunotherapy using checkpoint inhibitors, especially PD-1/PD-L1 inhibitors, has now evolved into the most promising therapy for cancer patients. However, most of these inhibitors are monoclonal antibodies, and their large size may limit their tumor penetration, leading to suboptimal efficacy. As a result, there has been a growing interest in developing low-molecular-weight checkpoint inhibitors. Here, we discover peptide-based anti-PD-L1 inhibitors to block the PD-1/PD-L1 interaction. These peptides exhibit high affinity and specificity to human PD-L1 as well as PD-L1-positive human cancer cells. Molecular docking studies indicate that the CLP002 peptide specifically binds to PD-L1 at the site where PD-L1 interacts with PD-1. The CLP002 peptide inhibits tumor growth and increases survival of CT26 tumor-bearing mice, suggesting that the CLP002 peptide represents a promising low-molecular-weight checkpoint inhibitor for cancer immunotherapy.
Kun Cheng, PhD, University of Missouri – Kansas City