# Project 3 Immunotherapeutic Targeting of SLC45A2 for Treatment of Uveal Melanoma

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $416,783

## Abstract

Project 3: Project Summary/Abstract
While novel immunotherapy regimens show promise in treating cutaneous melanoma, effective therapies for
advanced uveal melanoma remain a clear unmet need in the field for a disease that is highly treatment
refractory and leads to dismal patient survival rates. Adoptive cell therapy (ACT) is a form of immunotherapy
with strong potential to improve the outcome for uveal melanoma patients. ACT involves the ex vivo isolation
and expansion of antigen-specific, tumor-reactive T cells that are infused into the patient with the aim of
mediating disease regression and maintaining a durable response. Our group has demonstrated that longer
persistence of adoptively transferred cytotoxic T lymphocytes (CTL) in patients with cutaneous melanoma
correlates with improved clinical response, and we have accordingly developed an in vitro process using IL-21
to generate long-lived central memory-type T cells whose in vivo survival extends up to years from the time of
infusion. Following our crucial identification of an epitope of the melanoma-associated transporter protein
SLC45A2 that is highly expressed in uveal melanoma cells but not in normal melanocytes and capable of
eliciting a potent cytotoxic response against uveal melanoma cell lines, we will evaluate this epitope and
search for others within the same protein that can mediate adoptively transferred CTL-driven uveal melanoma
disease regression. Specifically, we propose a Phase I study in which we will determine the safety and clinical
efficacy of ACT targeting SLC45A2 in patients with metastatic uveal melanoma. This study will include a dose-
escalation cohort of SLC45A2-specific CTL primed by IL-21 to enrich for central-memory-like CD8 T cells,
followed by an expansion cohort of the same CTL at a dose without limiting toxicities in combination with
CTLA4 blockade (ipilimumab). We have previously demonstrated the ability of this combination to achieve
complete, durable responses with strong T cell persistence and antigen-spreading in refractory metastatic
melanoma. To evaluate the study, we will measure in vivo persistence of transferred SLC45A2-specific T cells
at weekly intervals and correlate with clinical response, and additionally assess induction of a multivalent T cell
response through antigen-spreading. Finally, in an effort to expand the number of melanoma patients eligible
for SLC45A2-targeted immunotherapy, we will, 1) identify additional epitopes from this protein that may be
presented by other prevalent HLA class allotypes, and 2) search for HLA class II-restricted peptides from
SLC45A2 to boost helper T cell-mediated amplification of the anti-tumor immune response. These studies
represent a critical new avenue for uveal melanoma treatment using targeted immunotherapy, which holds the
potential to improve patient survival for this challenging malignancy.

## Key facts

- **NIH application ID:** 10415940
- **Project number:** 5P50CA221703-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Cassian Yee
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $416,783
- **Award type:** 5
- **Project period:** 2019-07-16 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415940

## Citation

> US National Institutes of Health, RePORTER application 10415940, Project 3 Immunotherapeutic Targeting of SLC45A2 for Treatment of Uveal Melanoma (5P50CA221703-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10415940. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*