# Pre-clinical testing of a novel immunotherapy for HTLV-induced neurologic disease

> **NIH NIH R01** · DREXEL UNIVERSITY · 2021 · $431,433

## Abstract

Worldwide, 20 million people are infected with HTLV-1, a majority of which remain asymptomatic carriers (ACs)
while others develop ATL or HAM/TSP with no effective treatment, vaccine or cure. The exact mechanism(s) of
disease pathophysiology remain unresolved with a big question of high proviral load in HAM/TSP patients
despite vigorous cellular immune response (primarily directed towards viral transactivator protein Tax)? Our
initial studies implicated programmed death (PD)-1 receptor and its ligand, PD-L1 as potential underlying
factors for observed immune cells' dysfunctions leading to viral persistence and disease progression, primarily
in HAM/TSP patients. PD-1:PD-L1/PD-L2 are the members of immunoglobulin superfamily (IgSF) co-signaling
molecules and have been linked with CD8 T-cell exhaustion during chronic viral infections. Several members
of this family play critical role in regulating antigen-specific immune responses, and it is becoming increasingly
evident that blocking multiple inhibitory receptors simultaneously improves T-cell based therapies. Therefore,
we propose to investigate a comparative co-expression pattern of key IgSF negative regulators among carriers
versus patients followed by standardizing of a blockade strategy to restore polyfunctionality, immune
homeostasis, and cytolytic potential of antigen-specific T cells in HTLV-1 patient cohorts. To project advantage,
this kind of therapeutic measure has shown promising results in other human diseases; however, it needs to
be evaluated with respect to neuroinflammatory diseases especially those associated with chronic infection for
which HTLV-1 provides a good model. While this approach should help in restoring functions of pre-existing
antiviral immunity in patients, activating new CTLs to mimic polyclonal CD8 T-cell response found in ACs will
be the key for a successful immunotherapeutic intervention of HTLV-associated diseases. Thus, we will identify
a panel of HTLV-1 epitopes directly from the infected cells and validate in ACs to select potential neoepitopes
capable of initiating a polyclonal response in chronically infected patients. The selected candidates from both
approaches will then be coupled in a combined immunotherapy, which will be evaluated pre-clinically in a
humanized (BLT) mouse model of HTLV-1 chronic infection. Our central hypothesis is that a combined
immunotherapy coupled with immune checkpoint blockers and neo-epitopes derived from infected
cells will restore existing T-cell functions while expanding protective CTLs in chronically infected
patients. As a result of this, HTLV-1 proviral load and concomitant Tax expression will be reduced leading to
decreased antigen threshold for the expansion of T cells with dysregulated functions and exhausted
phenotype. The restoration of positive immunity within periphery will also lead to the reduced accumulation of
activated T cells and inflammation within the CNS potentially ameliorating the disease. These studies...

## Key facts

- **NIH application ID:** 10055787
- **Project number:** 5R01NS097147-05
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Pooja Jain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $431,433
- **Award type:** 5
- **Project period:** 2016-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055787

## Citation

> US National Institutes of Health, RePORTER application 10055787, Pre-clinical testing of a novel immunotherapy for HTLV-induced neurologic disease (5R01NS097147-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10055787. Licensed CC0.

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