---
title: "Tumour-selective CD20 expression enables rituximab repurposing for solid tumour immunotherapy"
id: "pubmed-42671316"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42671316"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42671316/"
doi: "10.1002/ctm2.70804"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Tumour-selective CD20 expression enables rituximab repurposing for solid tumour immunotherapy
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42671316
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42671316/)
- **DOI:** [10.1002/ctm2.70804](https://doi.org/10.1002%2Fctm2.70804)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Background: Antigen loss, downregulation, and off-tumour toxicity limit current solid tumour immunotherapies that depend on native tumour antigens. The authors propose an alternative strategy to bypass those antigen-related barriers. - Strategy: The study describes a tumour-targeted antigen programming (TRAP) approach that uses an NF-κB–responsive promoter to drive ectopic expression of the clinically validated antigen **CD20** selectively in tumour cells. - Delivery: Ectopic CD20 was delivered to tumours using adeno-associated virus (AAV) vectors under control of an **NF-κB**-specific promoter to restrict expression to tumour tissue. - Therapeutic repurposing: Following TRAP-mediated CD20 expression, tumours were treated with the anti-CD20 monoclonal antibody **rituximab**, a clinically validated antibody in hematologic malignancies. - Effector mechanisms: Rituximab engagement of ectopically expressed CD20 activated multiple antibody-dependent effector pathways, including **ADCC** (natural killer cell–mediated), **ADCP** (macrophage-mediated), and complement-dependent cytotoxicity (**CDC**). - Models tested: The approach was validated across multiple systems: cultured variant cancer cells, HCT116 3D spheroids, patient-derived organoids from human colorectal cancer, a humanized mouse bearing HCT116 xenografts, and an immunocompetent mouse with an MC38 transplant. - Specificity and efficacy: CD20 expression was reported as tumour-selective in vitro and in vivo, producing high cancer-cell specificity and resulting in substantial antitumour efficacy in the tested models. - Implication: TRAP repurposes both a clinically validated antigen and an approved therapeutic antibody to create a new immune-redirection modality for solid tumours, potentially overcoming antigen heterogeneity and off-tumour toxicity. - Limitations / reporting: The abstract and PubMed entry summarize outcomes and models but do not report numeric efficacy measures, safety data, dosing regimens, or long-term follow-up in the source record provided.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 School of Biological Science and Medical Engineering, Southeast University, Nanjing, China. * 2 Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. * 3 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. * PMID: **42671316** * DOI: [ 10.1002/ctm2.70804 ](https://doi.org/10.1002/ctm2.70804) Item in Clipboard # Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy Ziyan Kong et al. Clin Transl Med. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Clin Transl Med Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Clin+Transl+Med%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Clin+Transl+Med%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) . 2026 Sep;16(9):e70804. doi: 10.1002/ctm2.70804. ### Authors [Ziyan Kong](https://pubmed.ncbi.nlm.nih.gov/?term=Kong+Z&cauthor_id=42671316)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-1 "School of Biological Science and Medical Engineering, Southeast University, Nanjing, China."), [Yile Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42671316)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-1 "School of Biological Science and Medical Engineering, Southeast University, Nanjing, China."), [Yunqi Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+Y&cauthor_id=42671316)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-1 "School of Biological Science and Medical Engineering, Southeast University, Nanjing, China."), [Lu Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42671316)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-2 "Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China."), [Zhimin Fan](https://pubmed.ncbi.nlm.nih.gov/?term=Fan+Z&cauthor_id=42671316)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-2 "Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China."), [Yongqian Shu](https://pubmed.ncbi.nlm.nih.gov/?term=Shu+Y&cauthor_id=42671316)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-3 "Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China."), [Jinke Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+J&cauthor_id=42671316)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42671316/#short-view-affiliation-1 "School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.") ### Affiliations * 1 School of Biological Science and Medical Engineering, Southeast University, Nanjing, China. * 2 Jiangsu Clinical Innovation Center for Anorectal Diseases of T.C.M, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. * 3 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. * PMID: **42671316** * DOI: [ 10.1002/ctm2.70804 ](https://doi.org/10.1002/ctm2.70804) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Despite the clinical success of cancer immunotherapies, their efficacy is often compromised by antigen-related problems, including downregulation, loss, and off-tumour toxicity. **Methods:** To overcome these limitations that challenge the current immunotherapies dependent on native antigens, we here describe a new cancer immunotherapy strategy that artificially and specifically expresses a clinically validated antigen on variant tumours and thus repurposes clinical antibody drugs to treat cancers not belonging to their indications. To authenticate the strategy, we delivered a CD20 gene under the control of an NF-κB-specific promoter to tumours by adeno-associated virus and then treated them with a CD20 antibody, rituximab. **Results:** We found that CD20 was selectively expressed in tumours, and subsequent rituximab treatment engaged multiple antibody-dependent effector mechanisms, including NK-cell-mediated ADCC and macrophage-mediated ADCP. We demonstrated that this strategy is effective not only in variant-cultivated cancer cells, HCT116 spheroids, and patient-derived organoids of human colorectal cancer, but also in a humanized mouse with an HCT116 xenograft and immunocompetent mouse with an MC38 transplant. The strategy showed high cancer cell specificity in both in vitro and in vivo models, resulting in high therapeutic efficacy. **Conclusion:** This strategy thus creates a new modality of cancer immune-redirection therapy by repurposing both the clinically validated antigen and antibody. **Key points:** TRAP enables tumour-selective ectopic expression of the clinically validated antigen CD20, overcoming antigen limitations in solid tumour immunotherapy. TRAP repurposes anti-CD20 antibodies to engage diverse immune effector mechanisms, including ADCC, ADCP, and CDC. TRAP demonstrates antitumour efficacy across cellular, 3D tumour spheroid, patient-derived organoid, and in vivo solid tumour models. **Keywords:** antibody; antigen; cancer; immunotherapy; repurpose. © 2026 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## References 1. 1. Tang L, Huang Z, Mei H, Hu Y. Immunotherapy in hematologic malignancies: achievements, challenges and future prospects. Signal Transduct Target Ther. 2023;8(1):306. 2. 1. Lu Y, Zhao F, Strategies to overcome tumour relapse caused by antigen escape after CAR T therapy. Mol Cancer. 2025;24(1):126. 3. 1. Schuster SJ, Huw L, Bolen CR, et al., Loss of CD20 expression as a mechanism of resistance to mosunetuzumab in relapsed/refractory B‐cell lymphomas. Blood. 2024;143(9):822‐832. 4. 1. Ang Z, Paruzzo L, Hayer KE, et al., Alternative splicing of its 5'‐UTR limits CD20 mRNA translation and enables resistance to CD20‐directed immunotherapies. Blood. 2023;142(20):1724‐1739. 5. 1. Majzner R, Mackall C, Tumor antigen escape from CAR T‐cell therapy. Cancer Discov. 2018;8(10):1219‐1226. Show all 71 references ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Antigens, CD20* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antigens%2C+CD20%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antigens%2C+CD20) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Antigens, CD20* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antigens%2C+CD20%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antigens%2C+CD20) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Ectopic Gene Expression* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Ectopic+Gene+Expression%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Ectopic+Gene+Expression) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Immunotherapy* / methods Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Immunotherapy%2Fmethods%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Immunotherapy) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Mice Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mice) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Neoplasms* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Neoplasms* / immunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Neoplasms%2Fimmunology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Rituximab* / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Rituximab%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Rituximab) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Rituximab* / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Rituximab%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Rituximab) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) ## Substances * Rituximab Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Rituximab%22%5Bnm%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=%22Rituximab%22) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) * Antigens, CD20 Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antigens%2C+CD20%22%5Bnm%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=%22Antigens%2C+CD20%22) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42671316/) ## Grants and funding * [ 62371126/National Natural Science Foundation of China ](https://pubmed.ncbi.nlm.nih.gov/?term=62371126%2FNational+Natural+Science+Foundation+of+China%5BGrants+and+Funding%5D&sort=date&sort_order=desc "All articles for grant 62371126/National Natural Science Foundation of China") [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM **Send To** * [Clipboard](https://pubmed.ncbi.nlm.nih.gov/42671316/) * [Email](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42671316%2F%23open-email-panel) * [Save](https://pubmed.ncbi.nlm.nih.gov/42671316/) * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42671316%2F%23open-bibliography-panel) * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42671316%2F%23open-collections-panel) * [Citation Manager](https://pubmed.ncbi.nlm.nih.gov/42671316/) [x] NCBI Literature Resources [MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) The
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