# PhI/II Study of CD8-Reduced T Cells for Treatment of MDS or AML IND17305  (12/30/2016)

> **NIH FDA R01** · H. LEE MOFFITT CANCER CTR & RES INST · 2021 · $239,750

## Abstract

CD4+ T cells control the immune response to viral infections and to nascent cancers. They provide specific
directions to immunologic effector cells including macrophages, B cells, natural killers, and CD8+ T cells, and
endow the adaptive immune system with the capacity to remember past encounters and to respond in a rapid,
coordinated, and sustained fashion. The cardinal event in the escape of tumors from immune surveillance is
the functional decapitation of tumor-specific CD4+ T cells, resulting in the paralysis, or “exhaustion”, of anti-
tumor effector cells. In the absence of CD4+ T cell help, tumor-specific CD8+ T cells upregulate expression of
an inhibitory receptor, PD-1, and become unable to secrete cytokines or to kill tumor targets. Monoclonal
antibodies that block PD-1 “release the brakes” on anti-tumor T cells. However, PD-1 blockade attacks a
symptom and not the cause of the escape from immune surveillance: the loss of CD4+ T cell help. There are
no known methods for reversing tolerance in a patient’s tumor specific CD4+ T cells. Fortunately, CD4+ T cells
from healthy donors can provide the same instructions to revive the endogenous anti-tumor immune response.
The effectiveness of this approach was shown in a recent trial in which standard chemotherapy plus 3 doses of
mismatched related donor lymphocyte infusions (DLI) produced a complete remission (CR) in 80% and two-
year disease-free survival of 39% compared to current therapy of 43% CR and 10% two-year disease-free
survival. However, the presence of CD8+ T cells in the DLI can be associated with unacceptable toxicities such
as sustained donor cell engraftment and lethal graft-versus-host disease (GVHD)., and the use of related
donors may foreclose the possibility of subsequent allogeneic stem cell transplantation from a family donor.
The Johns Hopkins University is collaborating with the sponsor of IND 17305 (Cellunova LLC) to develop CD8-
depleted, HLA-mismatched unrelated DLI for patients with myelodysplastic syndrome after failure of
hypomethylating agents (HMA) or patients with secondary acute myeloid leukema. Standard therapy
comprises cytarabine plus daunorubicin or idarubicin and induces CR in approximately 20-50% of patients,
who then become candidates for curative allogeneic stem cell transplantation. The proposed approach
minimizes the risk of GVHD and preserves the option of allogeneic stem cell transplantation from a family
donor. The first clinical trial will use a standard 3+3 design to establish the maximally tolerated dose (MTD) of
donor CD4+ T cells and provide an estimate of the CR rate at the MTD for the cohort of patients with MDS
failing HMA. The major toxicities to be monitored are toxicities of the CD8 depletion device and toxicities of the
donor lymphocytes. We anticipate that non-sustained engraftment of CD4+ T cells will be associated with an
acceptable safety profile at doses of lymphocytes that will be able to be harvested from an unstimulated,
unrelate...

## Key facts

- **NIH application ID:** 9776403
- **Project number:** 5R01FD006095-03
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** HANY ELMARIAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $239,750
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9776403

## Citation

> US National Institutes of Health, RePORTER application 9776403, PhI/II Study of CD8-Reduced T Cells for Treatment of MDS or AML IND17305  (12/30/2016) (5R01FD006095-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9776403. Licensed CC0.

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