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The co-delivery of adenovirus-based immune checkpoint vaccine elicits a potent anti-tumor effect in renal carcinoma.

ABSTRACT: Immune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine's therapeutic effect. Compared to the single Ad vaccine group, the subcutaneous tumor growth was significantly reduced in Ad-CAIX/Ad-PD-L1 combination group. Co-immunization of Ad-CAIX/Ad-PD-L1 enhanced the induction and maturation of CD11c⁺ or CD8⁺CD11c⁺ DCs in the spleen and tumor and promoted the strong tumor-specific CD8⁺ T cell immune responses. In vivo CD8 T cell deletion assay showed that the anti-tumor effect of the Ad-CAIX/Ad-PD-L1 vaccine was mainly dependent on functional CD8⁺ T cell immune responses. Furthermore, the Ad-CAIX/Ad-PD-L1 vaccine effectively inhibited tumor growth and lung metastasis in metastatic or orthotopic models. These results indicate that the combination strategy of the immune checkpoint vaccine shows promising potential as an approach for malignant tumor therapy.

SUBMITTER: Jiang N

PROVIDER: S-EPMC10403580 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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The co-delivery of adenovirus-based immune checkpoint vaccine elicits a potent anti-tumor effect in renal carcinoma.

Jiang Nan N Zheng Yanyan Y Ding Jiage J Wang Jiawei J Zhu Fei F Wang Meng M Sobhani Navid N Neeli Praveen P Wang Gang G Li Hailong H Zheng Junnian J Chai Dafei D

NPJ vaccines 20230804 1

Immune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine's therapeutic effect. Compared ...[more]

PMID: 37542081

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Project description:Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO3 microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.

Dataset Information

The co-delivery of adenovirus-based immune checkpoint vaccine elicits a potent anti-tumor effect in renal carcinoma.

Publications

The co-delivery of adenovirus-based immune checkpoint vaccine elicits a potent anti-tumor effect in renal carcinoma.

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