# Immunotherapy of Uveal Melanoma using PRAME Vaccine in Combination with Adoptive T Cell Therapy

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $218,011

## Abstract

Adoptive cellular therapy and therapeutic cancer vaccines have shown promise in solid tumor malignancies but
responses have generally been modest. By combining these two modalities in a rationally designed first-in-
human study, we propose to treat patients with a highly-defined T cell product (comprised of PRAME-specific
memory T cells) in combination with an antigen- specific vaccine (comprised of a curated cocktail of synthetic
long peptides) to augment and sustain the in vivo persistence of transferred PRAME-specific T cells. Addition
of an immune checkpoint inhibitor, (anti-CTLA4), further favorably modulates the tumor environment by
enabling un-fettered CD28 engagement of B7 (to expand the in vivo population of CD28-hi PRAME-specific
memory T cells), lowering the threshold of activation of endogenous tumor-reactive T cells (facilitating antigen-
spreading), and modulating inhibitory activity (by engaging CTLA4+ regulatory cells). This study, as proof of
concept for this triple T cell-based strategy, will be used to address a critical unmet need for patients with
metastatic uveal melanoma, and establish a versatile platform for targeting a broader range of tumor antigens
and tumor types. In this study, all 3 modalities (PRAME vaccine, ETC therapy and anti-CTLA), are reduced to
clinical practice and by using a highly-defined antigen-specific T cell population for adoptive therapy, allows for
rigorous immunologic analysis so that reasons for success or failure can be elucidated.
In an effort to enhance efficacy as well as broaden this approach to benefit a larger pool of patients, PRAME
epitopes presented by additional HLA Class I and II alleles will be identified. The results of the proposed
studies may lead to formal Phase II trials to assess true efficacy, development of a new treatment standard for
refractory metastatic uveal melanoma, and refinement of CD4 T cell and combined CD4 and CD8 T cell
strategies that can be incorporated into future clinical studies.
This proposal leverages the clinically-tested expertise in therapeutic cancer vaccines at ISA Pharma and the
pioneering development of ETC therapy in the Yee Lab to explore an opportunity that is timely and ideally
suited for an academic – industrial partnership.

## Key facts

- **NIH application ID:** 10669241
- **Project number:** 5R01CA266714-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Alexandra P Ikeguchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $218,011
- **Award type:** 5
- **Project period:** 2022-07-20 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10669241

## Citation

> US National Institutes of Health, RePORTER application 10669241, Immunotherapy of Uveal Melanoma using PRAME Vaccine in Combination with Adoptive T Cell Therapy (5R01CA266714-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10669241. Licensed CC0.

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