# Marrow-Infiltrating Lymphocytes

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2020 · $243,858

## Abstract

Project 2
Project Summary
Marrow infiltrating lymphocytes (MILs) represent an approach to adoptive T cell therapy (ACT) initially
developed to enrich for tumor specific T cells from the tumor microenvironment for hematologic malignancies.
Our central hypothesis is that intrinsic characteristics of activated tumor-specific marrow infiltrating
lymphocytes determine their efficacy. Strategies to augment their anti-tumor efficacy will focus on overcoming
their pre-expansion dysfunction and minimizing the induction of tolerance in vivo. These hypotheses will be
tested clinically in the context of ongoing or new clinical trials of MILs in patients with relapsed malignancies
after alloBMT and those with refractory myeloma as well in preclinical in vitro and murine models.
Accordingly, in Specific Aim 1, we will investigate if the efficacy of autoMILs can be augmented by
increasing their antigen-specificity or through checkpoint blockade. As a part of this aim we will: i)
conduct a pilot randomized phase I/II clinical trial in relapsed multiple myeloma (MM) to evaluate if PD-1
blockade can augment efficacy of autoMILS as ACT in patients with relapsed multiple myeloma; ii) quantify
tumor specific immunity and global immune responsiveness to assess overall efficacy. In Specific Aim 2, we
will determine the efficacy and mechanisms of activated patient-derived, allogeneic (allo)MILs in
augmenting anti-tumor immunity in patients relapsing post-allogeneic BMT. In this aim we will: i)
determine the clinical efficacy of alloMILs in patients relapsing after alloBMT and ii) characterize the
mechanisms of success and failure in patients with relapsed malignancy after alloBMT treated with alloMILs.
Finally, in Specific Aim 3, we will test the hypothesis that MILs anti-tumor activity can be enhanced by
overcoming inhibitory checkpoints, harnessing agonists of co-stimulation, and by activating the
STING pathway. In aggregate, the proposed research is significant in addressing an important unmet need
of reducing or treating relapsed disease following BMT through clinical studies as well as increasing the
overall understanding of mechanisms of antitumor immunity and developing innovative ACT strategies
utilizing MILs to augment antitumor immunity posttransplant.

## Key facts

- **NIH application ID:** 9932944
- **Project number:** 5P01CA225618-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Leo Luznik
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,858
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932944

## Citation

> US National Institutes of Health, RePORTER application 9932944, Marrow-Infiltrating Lymphocytes (5P01CA225618-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932944. Licensed CC0.

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