AIM Platform: A Novel Nano Artificial Antigen-Presenting Cell-Based Clinical System Designed to Consistently Produce Multi-Antigen-Specific T-Cell Products with Potent and Durable Anti-Tumor Properties

Abstract

Over the last decade, tremendous progress has been made in the field of adoptive cell therapy. The two prevailing modalities include endogenous non-engineered approaches and genetically engineered T-cell approaches. Endogenous non-engineered approaches include dendritic cell-based systems and tumor-infiltrating lymphocytes (TIL) that are used to produce multi-antigen-specific T-cell products. Genetically engineered approaches, such as T-cell receptor engineered cells and chimeric antigen receptor T cells are used to produce single antigen-specific T-cell products. It is noted by the authors that there are alternative methods to sort for antigen-specific T cells such as peptide multimer sorting or cytokine secretion assay-based sorting, both of which are potentially challenging for broad development and commercialization. In this review, we are focusing on a novel nanoparticle technology that generates a non-engineered product from the endogenous T-cell repertoire. The most common approaches for ex vivo activation and expansion of endogenous, non-genetically engineered cell therapy products rely on dendritic cell-based systems or IL-2 expanded TIL. Hurdles remain in developing efficient, consistent, controlled processes; thus, these processes still have limited access to broad patient populations. Here, we describe a novel approach to produce cellular therapies at clinical scale, using proprietary nanoparticles combined with a proprietary manufacturing process to enrich and expand antigen-specific CD8<sup>+</sup> T-cell products with consistent purity, identity, and composition required for effective and durable anti-tumor response.

AIM™ platform: A new immunotherapy approach for viral diseases

“…Cells were processed according to the NexImmune AIM platform to produce an ACT, as previously described (14). As previously described, on day 0, after CD4 + T cell depletion, CD8 + T cells were enriched on a CliniMacs Prodigy (Miltenyi Biotec) using AIM nanoparticles loaded with the peptides listed in Table 1 (12). The enriched cells were seeded into a G-Rex culture system (Wilson-Wolf Manufacturing) and expanded for 14 days.…”

“…Incorporation of magnetic based systems to generate infectious disease specific ACT have shown promise (6,7), for reasons including the reduction in the manufacturing time compared to other clinically tested methods (10,11). The AIM Enrichment and Expansion (E+E) system is a reproducible, closed manufacturing process that consistently produces T cells for ACT comprised of non-genetically engineered multiple antigen specific effector and long-lived memory T cells from autologous or allogeneic donor leukopaks (12). Two AIM ACT clinical trials are currently ongoing: one for relapsed/refractory multiple myeloma (MM) [NCT04505813] and another for acute myeloid leukemia (AML) [NCT04284228].…”

Nanomedicine for Immunotherapy Targeting Hematological Malignancies: Current Approaches and Perspective

“…NEXI-001 T-cell product will be administered to AML subjects with refractory/relapsed disease after getting an allogenic stem cell transplant (www.ClinicalTrials.gov, accessed on 5 September 2021 identifier: NCT04284228). Subjects recruited in this study will have AML tumor-specific CD8+ T cells generated from the HLA-matched stem cell donor peripheral blood mononuclear cells [90]. The main goals for this study include safety and tolerability.…”

“…A second trial is actually recruiting relapsed/refractory MM subjects that have received at least three previous lines of treatment (www.ClinicalTrials.gov, accessed on 5 September 2021 identifier: NCT04505813). Analogously, the objective of this trial is to assess safety and tolerability [90].…”

Antigen-Presenting Cells: Potential of Proven und New Players in Immune Therapies

“…Engineered MHC class I-deficient K562 cells or paramagnetic nanoparticle-based artificial (a) APCs were designed to optimize and control T-cell signals required for activation, expansion, and costimulation via human leukocyte antigen-restricted peptide complex and costimulatory signals [26, 27]. These tools make the generation of APCs cost-effective, highly reproducible, and scalable, and generated T-cell products will be capable of generating potent and durable responses in treated patients [28-30]. Interestingly, genetically modified K562-based aAPCs were recently used as an inexhaustible source for CD19-directed chimeric antigen receptor (CAR) T-cell expansion, thereby opening up new areas of APC application [31].…”