What question did this study set out to answer?

To develop and evaluate a bispecific antibody capable of selectively targeting tumor cells presenting low-density neoantigens derived from the common TP53 R175H mutation.

March 1, 2021ScienceOpen Access

Targeting a neoantigen derived from a common TP53 mutation

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Authors

EHEmily Han-Chung Hsiue KWKatharine M. Wright JDJacqueline Douglass

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Overview

Preclinical study demonstrates targeted T-cell lysis of TP53-mutant cancer cells via a bispecific diabody, suggesting a viable immunotherapy strategy for previously undruggable cancer mutations.

Key Points

To develop and evaluate a bispecific antibody capable of selectively targeting tumor cells presenting low-density neoantigens derived from the common TP53 R175H mutation.
Identified and structurally characterized an antibody highly specific for the TP53 R175H peptide complexed with human leukocyte antigen-A (HLA-A) on the cell surface.
Engineered the antibody into a T-cell-engaging bispecific single-chain diabody.
Evaluated neoantigen recognition, T-cell activation, and cancer cell lysis in vitro and in mouse tumor models.
The antibody demonstrated exquisite specificity for the low-abundance TP53 R175H–HLA-A complex, discriminating it from wild-type sequences.
The bispecific single-chain diabody efficiently activated T cells to induce specific lysis of neoantigen-expressing cancer cells both in vitro and in vivo despite extremely low cell-surface antigen density.

Cite This Study

Hsiue et al. (2021) studied this question.

synapsesocial.com/papers/69d78d00ef4aa71f97f319e3 https://doi.org/10.1126/science.abc8697

View Full Paper

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March 1, 2021ScienceOpen Access

Targeting a neoantigen derived from a common TP53 mutation

View Full Paper

Ask AI

Bookmark

Authors

EHEmily Han-Chung Hsiue KWKatharine M. Wright JDJacqueline Douglass

Discussion

Member takes

Overview

Preclinical study demonstrates targeted T-cell lysis of TP53-mutant cancer cells via a bispecific diabody, suggesting a viable immunotherapy strategy for previously undruggable cancer mutations.

Key Points

To develop and evaluate a bispecific antibody capable of selectively targeting tumor cells presenting low-density neoantigens derived from the common TP53 R175H mutation.
Identified and structurally characterized an antibody highly specific for the TP53 R175H peptide complexed with human leukocyte antigen-A (HLA-A) on the cell surface.
Engineered the antibody into a T-cell-engaging bispecific single-chain diabody.
Evaluated neoantigen recognition, T-cell activation, and cancer cell lysis in vitro and in mouse tumor models.
The antibody demonstrated exquisite specificity for the low-abundance TP53 R175H–HLA-A complex, discriminating it from wild-type sequences.
The bispecific single-chain diabody efficiently activated T cells to induce specific lysis of neoantigen-expressing cancer cells both in vitro and in vivo despite extremely low cell-surface antigen density.

Cite This Study

Hsiue et al. (2021) studied this question.

synapsesocial.com/papers/69d78d00ef4aa71f97f319e3 https://doi.org/10.1126/science.abc8697

View Full Paper

Ask AI

Bookmark