Service Project # 1: Optimization of artificial antigen presenting cells (aAPCs) in pre-clinical models
Collaborating Investigator: Scott Carmer
Affiliation: CEO – NexImmune, Inc. Gaithersburg, MD
Funding Status: Neximmune, Inc.
Project Period: 01/01/18-12/31/20
The goal of SP #1 is to synthesize and validate artificial antigen presenting cells (aAPC) in preclinical AML models. For SP #1, we will push our engineered optimized aAPC, from SA1, for expansion of human CD8+ T cells which will be tested by NexImmune using their proprietary AML-specific antigens as well as shared AML antigens. In addition PLGA and other biocompatible aAPC developed in TR&D2 will be provided to NexImmune for their in vivo animal testing studies.
Specific Aim 1. Production and in vitro validation of aAPC particles based on iron dextran, and PLGA bead matrices (standard aAPC particles to be supplied by JHU). aAPC particles using iron dextran and PLGA matrices will be provided. Each matrix will be used to produce aAPC particles directed against the following AML targets, WT-1, PRAME, RHAMM and proprietary Neximmune identified antigen. The particles will be tested for functionality in T cell stimulation assays and populations will be phenotypically and functionally characterized. Long terms storage stability will be assessed by T cell proliferation assays.
Specific Aim 2. In Vivo efficacy studies oon PLGA and PLGA/PBAE based aAPC. These studies will be done using the murine B16 F10 melanoma model. As part of this Service Project, the Schneck lab along with Green lab will provide particles and expertise for protein coupling to nanoparticles
To develop an aAPC particle that is suitable for clinical development, NexImmune has conducted extensive research into synthetic biocompatible and biodegradable matrices that can be surface modified. Two synthetic matrices have been selected for this application. Iron dextran Beads – Iron dextran beads are iron (III)-hydroxoid-dextran, biocompatible beads. Similar beads (InFed®, Dexferrum®) are FDA approved for parental administration for iron deficiency at much higher doses than proposed for cancer immunotherapy. Iron dextran beads have been validated in human studies and are available as cGMP-compliant products. We will cross-reference Miltenyi’s FDA master file. In preliminary studies we tested Iron dextran bead-based aAPC particles and demonstrated that they could induce antigen-specific T cells in vitro. In this SP new Signal 2 particle will be also be provided and tested on our AML-associated antigens. NexImmune will also get PLGA/PBAE blends with Drs. Schneck and Green to generate PLGA/PBAE-based aAPC particles to mdel in vivo injection of aAPC.