Service Project # 1: Optimization of Artificial Antigen Presenting Cells (aAPCs) in Pre-Clinical Models
Collaborating Investigator: Kristi Jones
Affiliation: CEO – NexImmune, Inc. Gaithersburg, MD
Funding Status: Neximmune, Inc.
Project Period: 01/01/22-12/31/25
Summary
The goal of SP #1 is to synthesize and validate artificial antigen presenting cells (aAPC) in pre-clinical AML models. For SP #1, we will push our engineered optimized nano-aAPC and MP hydrogel-based aAPC, from TR&D1, for expansion of human CD8+ T cells and these will be tested using NexImmune proprietary AML-specific antigens as well as shared AML antigens. In addition LEAQ and other biocompatible polymeric particles developed in TR&D2 will be provided to NexImmune for incorporation into aAPCs for in vivo animal testing studies.
Approach
Specific Aim 1. Production and in vitro validation of aAPC particles based on iron dextran, and polymeric bead matrices (standard aAPC particles to be supplied by JHU). aAPC particles using iron dextran and polymeric matrices will be provided. Each matrix will be used to produce aAPC particles directed against the following AML targets, WT-1, PRAME, RHAMM and Survivn. 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 using intracellular cytokine production and T cell proliferation assays.
Specific Aim 2. In Vivo efficacy studies on Iron dextran and polymeric based particles. These studies will be done using the murine B16 F10 melanoma model. As part of this Service Project, the both TR&D1 and TR&D2 will provide particles and participate.
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 this SP new Signal 2 particle will be also be provided and tested on our AML-associated antigens. NexImmune will also get LEAQ NIM materials from TR&D2 to generate LEAQ-based aAPC particles to model in vivo applications.