# Class II artificial antigen presenting cells for cancer immunotherapy

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2022 · $28,676

## Abstract

Project Summary
 Adoptive cell therapy (ACT) has become an increasingly attractive method for treating
patients with solid tumors due to its impressive response rate; that said, the costs and
complexity of current cellular approaches for expansion of tumor-specific T cells have limited
accessibility of this therapy. Significant progress has been made in scalable, acellular
technologies for expanding tumor-specific CD8 T cells. However, no analogous acellular
platforms for expansion of CD4 T cells exist, despite overwhelming preclinical and clinical
evidence that CD4 T cells are central to antitumor immune responses and can augment CD8-
based therapies. The goal of the proposed project is to investigate the application of a novel
Class II artificial antigen presenting cell (aAPC) for expansion of functional, polyclonal
endogenous tumor-specific CD4 T cells for ACT as well as potential synergies with endogenous
CD8 T cells. The platform, which consists of a 50 nm paramagnetic iron dextran nanoparticle
conjugated with Class II Major Histocompatibility Complex proteins and costimulatory
molecules, will allow us 1) to enrich and expand rare murine and human tumor-specific CD4 T
cells to clinically relevant levels, and 2) to facilitate dendritic cell (DC) independent T cell help. In
turn, the Class II aAPC will allow us for the first time to monitor both the antitumor efficacy and T
cell receptor dynamics of ACT with polyclonal CD4 or combined CD4 and CD8 T cells in mice.
 To accomplish these goals, the project will proceed in three phases. First, we will
investigate the in vitro function and in vivo antitumor efficacy of aAPC-expanded polyclonal CD4
T cells specific to foreign and self-antigens, OVA and Trp1 with B16-OVA and B16-F10
melanoma models, respectively. Second, we will apply a modular human Class II aAPC,
capable of expanding a range of antigen-specific CD4 T cells through HLA molecules loaded
with thrombin-cleavable peptides, to expand functional tumor-antigen NY-ESO-1 specific CD4 T
cells from HLA DR1 and DP4 donors. Finally, we will combine the Class I and Class II aAPC
technologies to investigate DC independent in vitro and in vivo antitumor synergies of combined
antigen-specific mouse and human CD4 and CD8 culture, using B16-OVA and B16-F10 for
mouse T cells, and the human SK-MEL-37 (A2+/NY-ESO-1+) melanoma cell line for human T
cells. If successful, this proposal will deliver a novel acellular approach for polyclonal CD4 or
combined CD4 and CD8 ACT and will provide insight into alternative mechanisms of T cell help,
with potential clinical ramifications for ex vivo CD8 T cell expansion.

## Key facts

- **NIH application ID:** 10331830
- **Project number:** 5F31CA254121-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ariel Yosef Isser
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,676
- **Award type:** 5
- **Project period:** 2021-01-19 → 2022-06-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331830

## Citation

> US National Institutes of Health, RePORTER application 10331830, Class II artificial antigen presenting cells for cancer immunotherapy (5F31CA254121-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10331830. Licensed CC0.

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