We are excited to share our lab’s first research article! We have developed Transferrin Receptor Targeting Chimeras (TransTACs), a novel class of heterobispecific antibodies designed for targeted degradation of membrane proteins.

RT @HarvardCCB: New from the @brian_b_liau Lab, two papers in @Nature that reveal a chemical-genetic convergence #chemtwitter #CancerResear….

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We absolutely loved seeing this video explaining our TransTAC technology for targeted membrane protein degradation!! Hoping TransTAC opens doors to new cancer therapies and more!.

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RT @DanaFarber: Xin Zhou, PhD, a researcher at Dana-Farber and her team have developed a new platform that repurposes a cancer cell's own r….

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RT @DFCI_CancerBio: Congratulation on a beautiful paper @xinzhoulab!!!.

Our work was inspired by the groundbreaking LYTAC and AbTAC approaches, and we’re excited to join the rapidly growing field of extracellular targeted protein degradation (eTPD) to explore its potential in addressing unmet biomedical needs.

We’re grateful for the collaborative and supportive environment at @DFCI_CancerBio, @DFCI_ChemBio, and @HMS_BCMP, and for all current Zhou lab members, summer students, and rotation students for the fun discussions and brainstorming!.

We want to thank all the co-authors for their hard work, including Dr. Pasi Jänne and Jänne lab members for the inspiring discussions on lung cancer. We’re also deeply appreciative of our colleagues for their valuable input on identifying targets and clinical needs.

Our future research will focus on optimizing TransTAC designs for enhanced efficacy across a wider range of membrane protein families and cancer types, and exploring the potential of TransTACs in other disease contexts.

TransTAC offers a new strategy for controlling membrane proteins. Its high degradation efficacy, modularity, recombinant nature, tumor-targeting capability, and broad tissue coverage suggest its wide potential in cancer targeting and other biomedical applications.

EGFR-TransTAC significantly inhibited tumor growth in a xenograft model, with some mice showing near-complete tumor regression. It also demonstrated favorable PK, safety, and tissue distribution , highlighting its potential as a therapeutic candidate for EGFR-driven lung cancers.

To address this, we engineered EGFR TransTACs, which potently inhibited growth of tyrosine kinase inhibitor-resistant lung cancer cell lines (EGFR Del19/T790M/C797S) with higher cancer specificity.

Acquired resistance is a critical challenge in targeted therapy for many cancers including non-small cell lung cancer, with nearly all patients who receive tyrosine kinase inhibitors (TKIs) eventually developing resistance.

Building on this, we extended the approach to degrade several cancer targets, including EGFR-TransTAC for non-small cell lung cancer (NSCLC), CD20-TransTAC for lymphoma, PD-L1-TransTAC for regulating immunotherapy. TransTAC achieved >80% degradation in different cancer models.

We have successfully designed various TransTACs, starting with a chimeric antigen receptor (CAR)-TransTAC. CAR-TransTAC enabled reversible control of primary CAR-T cells, demonstrating their potential as an off-the-shelf switch for decreasing risk/improving safety of CAR therapy.

This approach leverages Transferrin Receptor 1 (TfR1), which is overexpressed in cancer cells due to their high iron demand. The rapid constitutive endocytosis of TfR1 enables precise TransTAC-mediated targeting and degradation of disease-associated proteins with high efficacy.

RT @John_E_Connolly: Love this approach @xinzhoulab Transferrin receptor targeting chimeras for membrane protein degradation | Nature http….