Abstract B63: Exploratory immune phenotyping of longitudinal blood samples from the first-in-human phase 1 clinical trial of a novel autologous cellular therapy in patients with metastatic solid tumors
Authors: Lederer James , Gargosky Sharron , Borriello Frank 
Published: December 2022

Abstract
Background: Alloplex Biotherapeutics has developed a novel autologous cellular immunotherapy that is prepared from patient PBMCs called SUPLEXA. SUPLEXA is a heterogeneous mixture of innate (e.g. NK, NKT cells) and adaptive immune cells (e.g. TCR ab and gd T cells) without B cells, Tregs, and myeloid lineage cells. SUPLEXA cells have been educated/trained ex vivo by melanoma cells that express an array of immunomodulatory factors. SUPLEXA cells acquire potent and broad tumor cell killing activity and will be given back to the patient as a cellular immunotherapy after expansion and cryopreservation.Methods: This clinical study is enrolling up to 40 participants in Australia in 2 cohorts: 1) Solid tumours, and 2) haematologic malignancies. The primary objective of this study is to assess safety and tolerability of SUPLEXA. The secondary objective is to assess the efficacy and changes in immune phenotypes or health occurring after SUPLEXA therapy. This abstract reports on exploratory findings from the first 3 patients enrolled in this study. All patients will receive a minimum of 3 weekly IV doses of 2.5 x 109 SUPLEXA therapeutic cells. Blood samples were taken at baseline and weekly intervals after SUPLEXA treatment. Plasma was prepared for cytokine profiling by a 40-plex Luminex cytokine panel and PBMCs were prepared for deep single-cell immunoprofiling by mass cytometry (CyTOF) using 48-marker antibody panels specific for all immune cell subsets. The aim of these exploratory studies is to determine changes in immune phenotype in patients given SUPLEXA therapy and to assess interpatient variability.Results: Patients 1 (squamous cell), 2 (ovarian), and 3 (ovarian) experienced no treatment associated adverse events and permission has been granted to continue enrolment. PBMC and SUPLEXA therapeutic cells were analysed by CyTOF and flow cytometry to measure immune phenotypes of these cell populations. Inter-patient variability was detected in PBMCs and SUPLEXA cells from the first 3 patients as anticipated. Immunoprofiling of baseline PBMCs and longitudinal PBMCs harvested at weekly time points after SUPLEXA treatments showed alterations in immune cell subset abundances as well as heterogeneity among patients. Profiling of multiple cytokines by Luminex indicated that SUPLEXA therapy altered the cytokine profiles in these first 3 patients with dramatic increases several the cytokines produced by SUPLEXA cells (IL-8 and Rantes).Conclusions: Immunophenotyping of circulating immune cells and cytokines from these 3 cancer patients provide the first longitudinal analysis of patients treated with SUPLEXA therapeutic cells. The immunophenotyping data already analysed suggest that SUPLEXA improved the immune health in these patients that also showed associated beneficial responses to SUPLEXA therapy. Since this clinical and research work is ongoing, up-to-date findings and correlations with clinical outcomes will be presented.
Citation Format: James Lederer, Sharron Gargosky, Frank Borriello. Exploratory immune phenotyping of longitudinal blood samples from the first-in-human phase 1 clinical trial of a novel autologous cellular therapy in patients with metastatic solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B63.