Peptide-MHC–targeted retroviruses enable in vivo expansion and gene delivery to tumor-specific T cells

TL;DR

Scientists developed a new method using virus-like particles to target and enhance tumor-fighting T cells directly in the body, potentially improving cancer treatments.

Contribution

A novel strategy using peptide-MHC-targeted retroviruses for in vivo activation and gene delivery to tumor-specific CD8 T cells is introduced.

Findings

pMHC-targeted viruses deliver function-enhancing cargos to CD8 T cells and activate them.

In vivo engineering of tumor-specific T cells using these viruses improves overall survival in mouse models.

The method enables efficient reprogramming and expansion of tumor-specific T cells directly in the body.

Abstract

Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated that endogenous T cells can be harnessed to initiate effective antitumor responses. Despite clinical promise, current TIL production protocols involve weeks-long ex vivo expansions that can affect treatment efficacy. Therefore, additional tools are needed to engineer TILs to have increased potency while mitigating manufacturing challenges. Here, we present a strategy for pseudotyping retroviruses with peptide–major histocompatibility complexes (pMHCs) for antigen-specific gene delivery to CD8 T cells and validate therapeutic impact in immunocompetent mouse models. We demonstrate that pMHC-targeted viruses specifically deliver function-enhancing cargos while simultaneously activating and expanding antitumor T cells. This targeting precision enables in vivo engineering of tumor-specific T cells, resulting in improved overall survival in B16F10-bearing mice. Together, we have established that pMHC-targeted viruses are efficient vectors for reprogramming and expanding tumor-specific T cells directly in vivo, with the potential to substantially streamline engineered cell therapy production.

Viral vectors displaying peptide-MHC are versatile tools for activating and reprogramming antitumor CD8 T cells directly in vivo.

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