Abstract 681: ICVB-1042, an oncolytic adenovirus, infects and kills bladder, breast, and glioblastoma human dissociated tumor cells
Authors: Pokrass Michael , Rosenthal Peter , Messinger Joshua , Field Jessica , Nowyhed Heba 
Published: April 2023

ICVB-1042 is a novel E2F transcription factor-dependent oncolytic virus (OV) demonstrated to confer tumor selective replication, enhanced potency and tumor tropism. The lytic efficiency of ICVB-1042 was assessed in human primary dissociated tumor cells (DTCs) from bladder, breast, and glioblastoma (GBM) tumors and compared against indication specific OVs. Primary DTCs were analyzed on xCELLigence eSight instrument for simultaneous imaging and viability monitoring. ICVB-1042 and comparator OVs were added at multiplicities of infection (MOI) ranging from 1.2 - 30; plates were cultured for 10 days. Cell index measurements quantified viability. Imaging for a viral-encoded reporter gene (YPet) expression quantified viral infection. Supernatant from infected samples was analyzed by ddPCR to quantify viral genome replication. Efficacy of ICVB-1042 was assessed in a PDX model of subcutaneous GBM in Nude mice, with intratumoral administration of ICVB-1042 every 3 days for 3 doses. Table 1 reports cytolysis data. Bladder: ICVB-1042 infection showed complete lysis at MOI 30 and impressive lysis at lower MOIs. Comparator showed high levels of lysis only at MOI 30. Breast: ICVB-1042 showed efficient lysis at all MOIs; comparator did not reach &gt;10% lysis in either donor. GBM: ICVB-1042 and comparator had similar lysis at MOI 30; ICVB-1042 showed efficient lysis at lower MOI. YPet imaging indicated ICVB-1042 infection spread more rapidly than comparators. ICVB-1042 produced more viral genomes via replication than comparators, particularly at high MOIs. ICVB-1042 showed significant tumor growth inhibition and increased overall survival compared to vehicle-treated animals. ICVB-1042 infection, replication, and cytolysis were evident across all diverse primary patient tumor types and multiple donor genotypes, with superior cytolysis compared to other indication specific OVs. ICVB-1042 maintains potent activity in vivo in patient GBM DCTs.

Table 1. - Percentage OV-Mediated Cytolysis of Primary Human DTCs by Indication, Donor, and MOI Indication Bladder Breast GBM Donor MOI ICVB-1042 Comparator OV-1 (E1A promoter swap for tumor selectivity; hGMCSF transgene expression) MOI ICVB-1042 Comparator OV-2 (Ad11/Ad3 chimera; Generated by directed evolution for tumor selectivity) MOI ICVB-1042 Comparator OV-3 (E1A mutation for tumor selectivity; RDG-4C fiber mutation for enhanced tropism) Donor 1 30 100% 89.2% 30 83.4% 8% 30 100% 97.3% 6 100% 0% 6 90.7% 0% 7.5 100% 71.6% 1.2 68.6% 0% 1.2 62.3% 0% 1.88 86% 5.9% Donor 2 30 100% 94.4% 30 78% 6.9% 30 69.1% 53.9% 6 14.6% 0% 6 97.6% 9.6% 7.5 49.5% 0% 1.2 0% 0% 1.2 100% 8.8% 1.88 36.7% 0%

Citation Format: Michael Pokrass, Peter Rosenthal, Joshua Messinger, Jessica Field, Heba Nowyhed. ICVB-1042, an oncolytic adenovirus, infects and kills bladder, breast, and glioblastoma human dissociated tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 681.