Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models
Among the plethora of cancer immune evasion mechanisms, T-cell-inhibiting factors within the tumor microenvironment impose a major challenge for the development of novel immunotherapies. Strategies to overcome immunosuppression and remodel the TME are therefore urgently needed. Therapeutic cancer va...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2514040 |
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| author | Kimberly Pojar Diana Reckendorfer Judith Strauss Sarah Szaffich Sarah Ahmadi-Erber Timo Schippers Pedro Berraondo Klaus K. Orlinger Josipa Raguz Henning Lauterbach |
| author_facet | Kimberly Pojar Diana Reckendorfer Judith Strauss Sarah Szaffich Sarah Ahmadi-Erber Timo Schippers Pedro Berraondo Klaus K. Orlinger Josipa Raguz Henning Lauterbach |
| author_sort | Kimberly Pojar |
| collection | DOAJ |
| description | Among the plethora of cancer immune evasion mechanisms, T-cell-inhibiting factors within the tumor microenvironment impose a major challenge for the development of novel immunotherapies. Strategies to overcome immunosuppression and remodel the TME are therefore urgently needed. Therapeutic cancer vaccines based on engineered arenaviruses have been proven to generate potent tumor specific CD8+ T-cell responses in preclinical models and cancer patients. Despite signs of clinical activity as monotherapy, combination therapies are needed to further increase the therapeutic effect. To address this need, we evaluated the efficacy of recombinant vectors based on lymphocytic choriomeningitis virus encoding the T-cell stimulating cytokines IL-7, IL-12 and IL-15 with or without tumor-associated antigens. These vectors were tested in three different mouse tumor models (TC-1, MC-38 and B16.F10). Our results demonstrate that only IL-12 encoding vectors led to increased immunogenicity and efficacy, which, after systemic administration, was associated with adverse events. The safest and most potent regimen consisted of systemic vaccination with tumor antigen encoding vectors and local injection of IL-12-encoding vectors. A single round of this treatment regimen resulted in 86–100% tumor-free mice and warrants further investigation. |
| format | Article |
| id | doaj-art-3ca90c7fa52d4d92a9a6cbe5672d7d4e |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-3ca90c7fa52d4d92a9a6cbe5672d7d4e2025-08-20T02:23:27ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2514040Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor modelsKimberly Pojar0Diana Reckendorfer1Judith Strauss2Sarah Szaffich3Sarah Ahmadi-Erber4Timo Schippers5Pedro Berraondo6Klaus K. Orlinger7Josipa Raguz8Henning Lauterbach9Hookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, SpainHookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAHookipa Pharma Inc, New York, NY, USAAmong the plethora of cancer immune evasion mechanisms, T-cell-inhibiting factors within the tumor microenvironment impose a major challenge for the development of novel immunotherapies. Strategies to overcome immunosuppression and remodel the TME are therefore urgently needed. Therapeutic cancer vaccines based on engineered arenaviruses have been proven to generate potent tumor specific CD8+ T-cell responses in preclinical models and cancer patients. Despite signs of clinical activity as monotherapy, combination therapies are needed to further increase the therapeutic effect. To address this need, we evaluated the efficacy of recombinant vectors based on lymphocytic choriomeningitis virus encoding the T-cell stimulating cytokines IL-7, IL-12 and IL-15 with or without tumor-associated antigens. These vectors were tested in three different mouse tumor models (TC-1, MC-38 and B16.F10). Our results demonstrate that only IL-12 encoding vectors led to increased immunogenicity and efficacy, which, after systemic administration, was associated with adverse events. The safest and most potent regimen consisted of systemic vaccination with tumor antigen encoding vectors and local injection of IL-12-encoding vectors. A single round of this treatment regimen resulted in 86–100% tumor-free mice and warrants further investigation.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2514040Arenavirus vectorsartLCMVcancer immunotherapycancer vaccineIL-12intratumoral virotherapy |
| spellingShingle | Kimberly Pojar Diana Reckendorfer Judith Strauss Sarah Szaffich Sarah Ahmadi-Erber Timo Schippers Pedro Berraondo Klaus K. Orlinger Josipa Raguz Henning Lauterbach Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models OncoImmunology Arenavirus vectors artLCMV cancer immunotherapy cancer vaccine IL-12 intratumoral virotherapy |
| title | Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models |
| title_full | Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models |
| title_fullStr | Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models |
| title_full_unstemmed | Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models |
| title_short | Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models |
| title_sort | combining local cytokine delivery and systemic immunization with recombinant artlcmv boosts antitumor efficacy in several preclinical tumor models |
| topic | Arenavirus vectors artLCMV cancer immunotherapy cancer vaccine IL-12 intratumoral virotherapy |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2514040 |
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