# Autohistomagnetic Isolation of Tumor-reactive T-cells

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2020 · $62,393

## Abstract

Adoptive cell therapy of autologous tumor-infiltrating lymphocytes (TIL) can now mediate objective cancer
regression in 50% of patients with metastatic melanoma. While TIL therapy has made incremental
improvements over recent decades, the fundamental methodologies have not significantly changed despite
major advances in the field of immuno-oncology. Current protocols for TIL therapy focus on the ex vivo
expansion of TIL from resected tumor biopsies using high-dose interleukin-2 over many weeks. This is a time-
consuming and expensive process that limits the eligibility of many patients and reduces the number of cancer
treatment facilities capable of offering this life-saving therapy. The most important factors governing clinical
response are the anti-tumor reactivity of the final TIL infusion product, and the total number of TIL generated
for adoptive transfer. Current methodologies are torn between the need to expand TIL quickly to maintain a
“young” phenotype that avoids exhaustion and the induction of tolerance, and the need to enrich for tumor-
reactive TIL. We propose a novel technology called autohistomagnetic isolation (AHMI) that uses patient
tumor-derived antigen presentation complex to select for reactive TIL within the first 48 hours after biopsy. The
basic principle of this new methodology uses conformation-dependent antibodies to immunoprecipitate
heterotrimers of HLA or H2-Kb, β-2 microglobulin, and cognate peptide onto magnetic beads. The resulting
construct can then isolate tumor-reactive TIL from non-reactive TIL using any magnetic separation platform
among positively selected bulk TIL cultures. This will greatly reduce the time needed to generate TIL infusion
products, will result in a more potent and persistent TIL phenotype, reduce cost, and increase anti-tumor
reactivity. We propose to fully optimize AHMI and interrogate the subsequent TIL infusion product in a pre-
clinical murine model of TIL therapy, and in samples from patients with metastatic melanoma. The completion
of the studies proposed here will produce a fully functional prototype for mouse and human AHMI and lay the
groundwork necessary for clinical trials.

## Key facts

- **NIH application ID:** 10328320
- **Project number:** 7R21CA214285-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Adam William Mailloux
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $62,393
- **Award type:** 7
- **Project period:** 2018-03-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328320

## Citation

> US National Institutes of Health, RePORTER application 10328320, Autohistomagnetic Isolation of Tumor-reactive T-cells (7R21CA214285-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328320. Licensed CC0.

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