One CD4+TCR and One CD8+TCR Targeting Autochthonous Neoantigens Are Essential and Sufficient for Tumor Eradication.

ABSTRACT:

Purpose

To achieve eradication of solid tumors, we examined how many neoantigens need to be targeted with how many T-cell receptors (TCR) by which type of T cells.

Experimental design

Unmanipulated, naturally expressed (autochthonous) neoantigens were targeted with adoptively transferred TCR-engineered autologous T cells (TCR-therapy). TCR-therapy used CD8+ T-cell subsets engineered with TCRs isolated from CD8+ T cells (CD8+TCR-therapy), CD4+ T-cell subsets engineered with TCRs isolated from CD4+ T cells (CD4+TCR-therapy), or combinations of both. The targeted tumors were established for at least 3 weeks and derived from primary autochthonous cancer cell cultures, resembling natural solid tumors and their heterogeneity as found in humans.

Results

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SUBMITTER: Wolf SP 

PROVIDER: S-EPMC11018470 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature