# PyroTIMER Technology: Enabling T-Cell Persistence in Immunosuppressive Tumor Microenvironments

> **NIH NIH R44** · PYROJAS INC · 2024 · $748,337

## Abstract

Abstract
The challenge of effectively treating cancer is further complicated by the limitations of current CAR-T cell
therapies, especially when confronted with the immunosuppressive tumor microenvironment (TIME). Central to
this issue is the transforming growth factor-beta (TGF-β), which induces T cell exhaustion and curtails their
antitumor potency. Current methodologies to inhibit the TGF-β pathway have yielded suboptimal results due to
transient effects. This project introduces PyroTIMER CAR-T cells, an innovative approach that promises durable
inhibition of all TGF-β isoforms within the TIME. This robust strategy not only targets TGF-β with unprecedented
potency but also incorporates multiple technical advancements, enhancing T cell cytotoxicity and leveraging
patient-derived xenograft (PDX) models for a more accurate representation of the tumor milieu.
The overarching research plan is to thoroughly assess PyroTIMER CAR-T cells in both immunocompetent
syngeneic models and PDX models. Employing multi-parametric flow cytometry, we aim to delve into the immune
dynamics within tumors, elucidating how PyroTIMER CAR-T cells interact with and potentially remodel the TIME.
Our objectives are four-fold: 1. Deciphering the influence of TGF-β on PyroTIMER CAR-T cells. 2. Profiling
cytokine production to gauge risks, particularly concerning cytokine release syndrome (CRS). 3. Investigating
potential exhaustion scenarios in PyroTIMER CAR-T cells. 4. In-depth in vivo evaluations of the safety and
efficacy of PyroTIMER CAR-T cells.
Our long-term trajectory is underpinned by a commitment to patient safety and therapeutic efficacy. By forging
collaborations with pharmaceutical entities, refining manufacturing strategies for scalability, and seeking FDA
endorsement, we aspire to position PyroTIMER CAR-T cells at the forefront of personalized cancer therapies.
This initiative represents a harmonious blend of advanced scientific inquiry, patient well-being, and strategic
commercial planning. Through this endeavor, we aim to redefine CAR-T cell therapy, presenting a novel, potent,
and safer treatment paradigm for cancer patients.

## Key facts

- **NIH application ID:** 11008389
- **Project number:** 1R44CA295355-01
- **Recipient organization:** PYROJAS INC
- **Principal Investigator:** ARCHIS BAGATI
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $748,337
- **Award type:** 1
- **Project period:** 2024-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11008389

## Citation

> US National Institutes of Health, RePORTER application 11008389, PyroTIMER Technology: Enabling T-Cell Persistence in Immunosuppressive Tumor Microenvironments (1R44CA295355-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11008389. Licensed CC0.

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