ArticleCancer discovery2023
Creating MHC-Restricted Neoantigens with Covalent Inhibitors That Can Be Targeted by Immune Therapy.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 69 citations in OpenAlex.
- Exploring the immunological effects of antibody-drug conjugates.Nature reviews. Clinical oncology · 2026Review
- Expanding the repertoire of chemically induced covalent neoantigens.Nature chemical biology · 2026Article
- Evolution of bispecific and multispecific antibodies in cancer therapy.The Lancet regional health. Europe · 2026Review
- KRAS Inhibitors in Pancreas Cancer: Facts and Hopes about the Immunotherapy We Have All Been Waiting for.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Molecular origin, discovery, validation and application of neoantigens.Asian journal of pharmaceutical sciences · 2026Review
- Lysine Targeting Group-Transfer Chimeras for Proximity Induction.Angewandte Chemie (International ed. in English) · 2026Article
- Engineered antibodies that stabilize drug-modified KRASNature communications · 2025Article
- PROTACs in cancer immunotherapy: a minireview.Biochemical Society transactions · 2025Review
- Emerging Therapeutic Approaches to Pancreatic Adenocarcinoma: Advances and Future Directions.Current treatment options in oncology · 2025Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Mechanisms and current advances in treatingChinese medical journal pulmonary and critical care medicine · 2025Review
- KRAS: the Achilles' heel of pancreas cancer biology.The Journal of clinical investigation · 2025Review
- Generation of actionable, cancer-specific neoantigens from KRAS(G12C) with adagrasib.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A pan-cancer atlas of therapeutic T cell targets.bioRxiv : the preprint server for biology · 2025Article
- Selective targeting of oncogenic hotspot mutations of the HER2 extracellular domain.Nature chemical biology · 2025Article
- Article
- Integrating epidemiology and genomics data to estimate the prevalence of acquired cysteine drug targets in the U.S. cancer patient population.The pharmacogenomics journal · 2025Article
- KRAS inhibitors: resistance drivers and combinatorial strategies.Trends in cancer · 2025Review
- Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C-MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies.Cancer research · 2025Article
Corrections and comments
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- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Intracellular oncoproteins can be inhibited with targeted therapy, but responses are not durable. Immune therapies can be curative, but most oncogene-driven tumors are unresponsive to these agents. Fragments of intracellular oncoproteins can act as neoantigens presented by the major histocompatibility complex (MHC), but recognizing minimal differences between oncoproteins and their normal counterparts is challenging. We have established a platform technology that exploits hapten-peptide conjugates generated by covalent inhibitors to create distinct neoantigens that selectively mark cancer cells. Using the FDA-approved covalent inhibitors sotorasib and osimertinib, we developed "HapImmune" antibodies that bind to drug-peptide conjugate/MHC complexes but not to the free drugs. A HapImmune-based bispecific T-cell engager selectively and potently kills sotorasib-resistant lung cancer cells upon sotorasib treatment. Notably, it is effective against KRASG12C-mutant cells with different HLA supertypes, HLA-A*02 and A*03/11, suggesting loosening of MHC restriction. Our strategy creates targetable neoantigens by design, unifying targeted and immune therapies. SIGNIFICANCE: Targeted therapies against oncoproteins often have dramatic initial efficacy but lack durability. Immunotherapies can be curative, yet most tumors fail to respond. We developed a generalizable technology platform that exploits hapten-peptides generated by covalent inhibitors as neoantigens presented on MHC to enable engineered antibodies to selectively kill drug-resistant cancer cells. See related commentary by Cox et al., p. 19. This article is highlighted in the In This Issue feature, p. 1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.