# Next Generation Autologous TIL Cancer Therapy: Development of GMP manufacturing process

> **NIH NIH R44** · TRAMPOLINE PHARMA, INC. · 2023 · $1,000,000

## Abstract

The overall goal of this Phase II SBIR grant proposal is to research and develop the GMP manufacturing
process for next-generation tumor infiltrating lymphocyte (TIL) cancer therapeutic for solid tumors. In clinical
trials, TIL-based immunotherapies have demonstrated tumor regression and increased survival rates against
different cancer types. Despite these encouraging clinical results, durable antitumor responses are typically
observed in a subset of patients with advanced cancers like melanoma. This stresses the need to develop
more effective TIL-based strategies and to expand efficacy against different cancer types. TIL therapies are
hindered in part by low TIL accumulation into tumors, low persistence, weak T cell receptor (TCR) affinity
and/or avidity as well as the low expression of tumor antigens on the cell’s surface. Additionally, the presence
of suppressive signals on T cells such as Lag3, Tim3, CD39, pose a major obstacle to generating effective and
long-lived antitumor T cell responses. In our published and preliminary studies, activating MyD88 signaling in
human or mouse T cells, increases antitumor activity and prolongs T cell survival. By fusing the high affinity
CD8α (extracellular) to MyD88 (intracellular; CD8α:MyD88) we have developed a novel and universal platform
that activates MyD88 signaling strictly upon the engagement of the TCR with the MHC-antigen on tumor cells.
CD8α:MyD88 expression in TILs cells substantially increases responses to weak and suboptimal levels of
tumor antigens including neoantigens, and in preliminary studies has demonstrated the extraordinary property
of reducing the T cells entry into an ‘exhausted state’. Importantly, the use of the CD8α co-receptor represents
a ‘universal’ approach to enhancing T cell responses, and can be used in patients regardless of the patient’s
HLA type. Through this SBIR Phase II application, we propose the following aims. Aim 1 will research,
develop, and manufacture GMP grade g-retroviral vectors. Here, we will generate high virus titer-producing
CD8a:MyD88-EGFRt PG-13 cell lines, accompanying analytical assays, and manufacture the GMP
CD8a:MyD88-EGFRt g-retroviral vectors. For this aim, we are partnering with a commercial contract
development manufacturing organization (CDMO), Vigene Biosciences to generate GMP viral vectors. In Aim
2, we propose to develop and manufacture GMP CD8a:MYD88 engineered TILs (coR8:AMPTM TILs). In
collaboration with the Gates Manufacturing Facility (GBF) at the University of Colorado Anschutz Medical
Campus (UCAMC) we will conduct process & analytical assay, QC release assay, develop and manufacture of
GMP grade coR8:AMPTM TILs. The successful completion of these aims will lead to the pre-IND and IND filings
with the FDA for a Phase I clinical trial in patients with immune refractory solid tumors. This activity will be
conducted in collaboration with the UCAMC’s Cell Therapy Operations Program (CTOP), Gates
Biomanufacturing Facility, and our te...

## Key facts

- **NIH application ID:** 10685604
- **Project number:** 5R44CA268313-02
- **Recipient organization:** TRAMPOLINE PHARMA, INC.
- **Principal Investigator:** RICHARD C DUKE
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,000,000
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685604

## Citation

> US National Institutes of Health, RePORTER application 10685604, Next Generation Autologous TIL Cancer Therapy: Development of GMP manufacturing process (5R44CA268313-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10685604. Licensed CC0.

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