Broadly applicable TCR-based therapy for multiple myeloma targeting the immunoglobulin J chain.

ABSTRACT:

Background

The immunoglobulin J chain (Jchain) is highly expressed in the majority of multiple myeloma (MM), and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM.

Methods

Using immunopeptidomics, we identified Jchain-derived epitopes presented by MM cells, and pHLA tetramer technology was used to isolate Jchain-specific T-cell clones.

Results

We identified T cells specific for Jchain peptides presented in HLA-A1, -A24, -A3, and -A11 that recognized and lysed JCHAIN-positive MM cells. TCRs of the most promising T-cell clones were sequenced, cloned into retroviral vectors, and transferred to CD8 T cells. Jchain TCR T cells recognized target cells when JCHAIN and the appropriate HLA restriction alleles were expressed, w

SUBMITTER: Meeuwsen MH 

PROVIDER: S-EPMC9969645 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature