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- Publisher Website: 10.1016/j.omto.2021.01.010
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Article: Eliminating mesothelioma by AAV-vectored, PD1-based vaccination in the tumor microenvironment
Title | Eliminating mesothelioma by AAV-vectored, PD1-based vaccination in the tumor microenvironment |
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Authors | |
Keywords | Adeno-associated virus TWIST1 antigen Mesothelioma PD-1 PD1-based vaccination Immune checkpoint blockade Immunotherapy T cell immunity |
Issue Date | 2021 |
Publisher | Elsevier (Cell Press): OAJ. The Journal's web site is located at https://www.cell.com/molecular-therapy-family/oncolytics/current |
Citation | Molecular Therapy - Oncolytics, 2021, v. 20, p. 373-386 How to Cite? |
Abstract | The potency of cancer vaccines is often compromised by a variety of immunoinhibitory mechanisms, including stimulation of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint pathway. Here, to overcome inhibition, we determined the potential of recombinant adeno-associated virus (rAAV)-vectored, PD1-based vaccination in the tumor microenvironment (TME) to activate antigen-specific T cell responses in the immune-competent murine mesothelioma model. We found that our rAAV-soluble PD1 (sPD1)-TWIST1 vaccine elicited and maintained TWIST1-specific cytotoxic T lymphocyte (CTL) responses and the PD-1 blocker systemically against lethal mesothelioma challenge after intramuscular injection, which was more effective than rAAV-TWIST1 or rAAV-sPD1 alone. More importantly, intratumoral injection of rAAV-sPD1-TWIST1 significantly enhanced immune surveillance by inducing TWIST1-specific CTL responses against vaccine-encoded TWIST1 and bystander gp70-AH1 epitopes, increasing CTL infiltration into the TME and decreasing tumor-associated immunosuppression, leading to complete elimination of established mesothelioma in 5 of 8 tumor-bearing mice. In addition, direct oncosuppression synergized with recruitment of T cells after localized rAAV-sPD1-TWIST1 treatment in a humanized mouse model to inhibit growth of REN human mesothelioma. Our results warrant clinical development of the rAAV-sPD1-TWIST1 vaccine to enhance immunotherapy against a wide range of TWIST1-expressing tumors. |
Persistent Identifier | http://hdl.handle.net/10722/304491 |
ISSN | 2023 Impact Factor: 5.3 2023 SCImago Journal Rankings: 1.494 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Tan, Z | - |
dc.contributor.author | Chiu, MS | - |
dc.contributor.author | Yan, CW | - |
dc.contributor.author | Man, K | - |
dc.contributor.author | Chen, Z | - |
dc.date.accessioned | 2021-09-23T09:00:46Z | - |
dc.date.available | 2021-09-23T09:00:46Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Molecular Therapy - Oncolytics, 2021, v. 20, p. 373-386 | - |
dc.identifier.issn | 2372-7705 | - |
dc.identifier.uri | http://hdl.handle.net/10722/304491 | - |
dc.description.abstract | The potency of cancer vaccines is often compromised by a variety of immunoinhibitory mechanisms, including stimulation of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint pathway. Here, to overcome inhibition, we determined the potential of recombinant adeno-associated virus (rAAV)-vectored, PD1-based vaccination in the tumor microenvironment (TME) to activate antigen-specific T cell responses in the immune-competent murine mesothelioma model. We found that our rAAV-soluble PD1 (sPD1)-TWIST1 vaccine elicited and maintained TWIST1-specific cytotoxic T lymphocyte (CTL) responses and the PD-1 blocker systemically against lethal mesothelioma challenge after intramuscular injection, which was more effective than rAAV-TWIST1 or rAAV-sPD1 alone. More importantly, intratumoral injection of rAAV-sPD1-TWIST1 significantly enhanced immune surveillance by inducing TWIST1-specific CTL responses against vaccine-encoded TWIST1 and bystander gp70-AH1 epitopes, increasing CTL infiltration into the TME and decreasing tumor-associated immunosuppression, leading to complete elimination of established mesothelioma in 5 of 8 tumor-bearing mice. In addition, direct oncosuppression synergized with recruitment of T cells after localized rAAV-sPD1-TWIST1 treatment in a humanized mouse model to inhibit growth of REN human mesothelioma. Our results warrant clinical development of the rAAV-sPD1-TWIST1 vaccine to enhance immunotherapy against a wide range of TWIST1-expressing tumors. | - |
dc.language | eng | - |
dc.publisher | Elsevier (Cell Press): OAJ. The Journal's web site is located at https://www.cell.com/molecular-therapy-family/oncolytics/current | - |
dc.relation.ispartof | Molecular Therapy - Oncolytics | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Adeno-associated virus | - |
dc.subject | TWIST1 antigen | - |
dc.subject | Mesothelioma | - |
dc.subject | PD-1 | - |
dc.subject | PD1-based vaccination | - |
dc.subject | Immune checkpoint blockade | - |
dc.subject | Immunotherapy | - |
dc.subject | T cell immunity | - |
dc.title | Eliminating mesothelioma by AAV-vectored, PD1-based vaccination in the tumor microenvironment | - |
dc.type | Article | - |
dc.identifier.email | Tan, Z: zwtan@hku.hk | - |
dc.identifier.email | Chiu, MS: carolcms@hku.hk | - |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.email | Chen, Z: zchenai@hku.hk | - |
dc.identifier.authority | Tan, Z=rp02817 | - |
dc.identifier.authority | Man, K=rp00417 | - |
dc.identifier.authority | Chen, Z=rp00243 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.omto.2021.01.010 | - |
dc.identifier.pmid | 33614918 | - |
dc.identifier.pmcid | PMC7878991 | - |
dc.identifier.scopus | eid_2-s2.0-85100663351 | - |
dc.identifier.hkuros | 325591 | - |
dc.identifier.volume | 20 | - |
dc.identifier.spage | 373 | - |
dc.identifier.epage | 386 | - |
dc.identifier.isi | WOS:000635158900031 | - |
dc.publisher.place | United States | - |