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A Viral Nanoparticle Cancer Vaccine Delays Tumor Progression and Prolongs Survival in a HER2⁺ Tumor Mouse Model.

ABSTRACT: Human epidermal growth factor receptor 2 (HER2) overexpression is associated with aggressive tumors with increased incidence of metastasis and recurrence. Therapeutic antibodies such as Trastuzumab inhibit tumor growth through blockade of HER2 receptors. However, the short lifespan of such therapeutic antibodies necessitates repeat administrations with ensuing cardiac toxicity and development of resistance, while offering no protection against relapse. Cancer vaccines targeting HER2 can overcome these shortcomings of passive immunotherapy by instigating an endogenous and sustained immune response and memory against the cancer antigen. The efficacy of a viral nanoparticle (VNP)-based cancer vaccine is demonstrated here in activating a potent anti-HER2 immune response that delays progression of primary tumors as well as metastases and prolongs survival in mice. The results illustrate that the VNP-based vaccine instigates HER2-specific antibodies as well as effector and memory T cells, which contributes to the effectiveness of the vaccine. Given the highly aggressive course of HER2⁺ cancers, inhibition of disease progression by such cancer vaccines could provide a critical window for interventions with other adjuvant therapies. Moreover, the immune memory generated by this viral nanoparticle-based cancer vaccine could mitigate relapse of the disease.

SUBMITTER: Shukla S

PROVIDER: S-EPMC8043622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3-L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3-L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.

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A Viral Nanoparticle Cancer Vaccine Delays Tumor Progression and Prolongs Survival in a HER2⁺ Tumor Mouse Model.

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A Viral Nanoparticle Cancer Vaccine Delays Tumor Progression and Prolongs Survival in a HER2+ Tumor Mouse Model.

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OmicsDI is part of the ELIXIR infrastructure

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A Viral Nanoparticle Cancer Vaccine Delays Tumor Progression and Prolongs Survival in a HER2⁺ Tumor Mouse Model.