Session Details

Presidential Plenary - CAR-Ts Beyond B Cells
Thursday, May 30, 2019 09:00 AM - 10:30 AM
Plenary Hall
CAR-T cell therapies for B-cell malignancies are now approved by regulators and governments in many advanced markets worldwide. They are changing lives and providing cures for those suffering with specific types of relapsed or refractory leukaemias and lymphomas. While CAR-T cells against B-cell markers are proven and will likely be used more widely for additional blood cell malignancies, progress to date concerning solid tumours has been less spectacular. In this session three outstanding clinician-scientists from three continents will discuss their various approaches to using cellular immune-gene therapies for non-B cell cancers. In the context of using CAR-T cells “beyond B Cells”, Dr Gill will discuss his approach to myeloid malignancies, Dr Han will provide data from his Phase 1 trial in mesothelin-positive cancers, and Dr Locatelli will outline his innovative strategy for neuroblastoma. The challenges required to overcome a less-conducive cellular microenvironment will also be defined.

CAR T Cells for Acute Myeloid Leukemia
Saar Gill MD, PhD, University of Pennsylvania, USA
In this presentation, I will review the reasons CAR T cell therapy for myeloid malignancies has lagged behind that for B-lymphoid malignancies and outline several potential ways to bring this potent therapeutic modality to patients.

Treatment of Autologous Mesothelin-targeted CAR T Cells with Genomic PD-1/TCR Deletion in Solid Tumor Patients
Weidong Han MD, PhD , Chinese PLA General Hospital, China
Experimental data both at cellular and tumor-bearing mice levels revealed an enhanced anti-tumor effect of mesothelin-redirected CAR T cells after deleting genomic PD-1, meanwhile this effect and the CAR T cell expansion capacity is not disrupted by TCR knock out. Then, dose-escalated mesothelin-PD1/TCR-KO-CAR T cell infusion (1× to 90×105/kg) regimen was translated into phase I clinical trial in advanced mesothelin+ solid tumor patients beginning from Feb. 2018 (NCT03545815). Infusion-related common adverse events including febrile syndrome, anaphylaxis, CRS, newly-presented cavity effusion were not observed, and the suspicious indications of autoimmune reaction were not perceived in all 16 patients. No aberrant implications unrelated to tumor progression were perceived as well. Six patients had experienced accrued effusions in tumor-infiltrated cavity within 3 weeks after cell infusions. CAR T cell monitoring showed a CAR-DNA copy number peak within 2 weeks and undetectable 4 weeks after infusions in PB; interestingly, TCR+, but not TCR- CAR+ T cells in effusions; sparsely detectable only in 2 tumor biopsies. DNA copy number comparison did not indicate a superior existence of CAR T cells in tumors than in PB. Combined data with clinical response implied an inferior anti-tumor activity of CAR T cells with PD-1 and/or TCR deletion.

Franco Locatelli MD, PhD , University of Pavia and IRCCS Ospedale Pediatrico Bambino Gesù, Italy