A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal Cancer Models

Yagiz, Kader; Rodriguez-Aguirre, Maria; Espinoza, Fernando Lopez; Montellano, Tiffany T.; Mendoza, Daniel; Mitchell, Leah; Ibañez, Carlos E.; Kasahara, Noriyuki; Gruber, Harry E.; Jolly, Douglas J.; Robbins, Joan M.

doi:10.1016/j.omto.2017.12.001

Cited by 28 publications

(23 citation statements)

References 55 publications

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“…Retroviral replicating vector (Tocagen, Toca-511, vocimagene amiretrorepvec) encodes yeast cytosine deaminase (CD) that transforms the prodrug 5-FC into the anticancer drug that can increase the local concentration of 5-FU in the tumor and decrease overall systemic toxicity of the drug. Different from the OVs discussed above, these vectors are non-lytic but, instead, selectively replicate in dividing cells with defective innate immunity and interferon responsiveness (80).…”

Section: Retrovirusmentioning

confidence: 99%

RETRACTED: The Oncolytic Virus in Cancer Diagnosis and Treatment

Cao

Sun

et al. 2020

Front. Oncol.

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Cancer has always been an enormous threat to human health and survival. Surgery, radiotherapy, and chemotherapy could improve the survival of cancer patients, but most patients with advanced cancer usually have a poor survival or could not afford the high cost of chemotherapy. The emergence of oncolytic viruses provided a new strategy for us to alleviate or even cure malignant tumors. An oncolytic virus can be described as a genetically engineered or naturally existing virus that can selectively replicate in cancer cells and then kill them without damaging the healthy cells. There have been many kinds of oncolytic viruses, such as herpes simplex virus, adenovirus, and Coxsackievirus. Moreover, they have different clinical applications in cancer treatment. This review focused on the clinical application of oncolytic virus and predicted the prospect by analyzing the advantages and disadvantages of oncolytic virotherapy.

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Section: Retrovirusmentioning

confidence: 99%

RETRACTED: The Oncolytic Virus in Cancer Diagnosis and Treatment

Cao

Sun

et al. 2020

Front. Oncol.

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“…Combining suicide and immune gene therapy in an aggressive melanoma model, together HSV-tk and GM-CSF induced a meaningful systemic immune response that was stronger as compared to GM-CSF alone [92]. The induction of an immune response upon CD/5-FC may be less well known [93] but has also been reported [94,95]. Adenoviral delivery of HSV-tk was tested in a phase III trial, showing increased time to death in patients with high-grade glioma, but it did not increase overall survival [96]; perhaps combining suicide gene therapy with an additional immunotherapy approach could improve response.…”

Section: Suicide Gene Therapymentioning

confidence: 99%

Gene-based Interventions for Cancer Immunotherapy

Cerqueira¹,

Silva²,

LunaVieira³

et al. 2019

In Vivo and Ex Vivo Gene Therapy for Inherited and Non-Inherited Disorders

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Immunotherapy of cancer has deservedly gained much attention in the past few years and is likely to continue to advance and become a fundamental cancer treatment. While vaccines, chimeric antigen receptor (CAR) T cells and checkpoint blockade have received the lion's share of the attention, an important direct role for gene transfer as an immunotherapy is emerging. For example, oncolytic viruses induce immunogenic cell death, thus liberating both antigens and the signals that are necessary for the activation of antigenpresenting cells, ensuring stimulation of an adaptive response. In another example, transfer of prodrug converting enzymes, such as the herpes simplex virus-thymidine kinase (HSV-tk) gene or the cytosine deaminase gene, has been shown to promote an immune response, thus functioning as immunotherapies. Alternatively, our own work involves the use of nonreplicating viral vectors for the simultaneous delivery of gene combinations that promote both cell death and an immune response. In fact, our gene transfer approach has been applied as a vaccine, immunotherapy or in situ gene therapy, resulting in immunogenic cell death and the induction of a protective immune response. Here, we highlight the development of these approaches both in terms of technical advances and clinical experience.

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“…(b) Peptide Vaccines. Peptide vaccines contain antigenic epitopes derived from TAAs, with the most commonly targeted peptides being carcinoembryonic antigen (CEA), EGFR, and mucin 1 [199]. In a phase II trial, only a limited benefit was observed when 96 patients with chemotherapy-resistant mCRC were treated with an oxaliplatin-based chemotherapy regimen combined with a vaccine containing 5 human leukocyte antigen (HLA)-A * 2402-restricted peptides of which 3 were from oncoantigens and 2 were from VEGF receptors [200].…”

Section: Adoptive Cell Transfer Adoptive Cell Therapy (Act)mentioning

confidence: 99%

Expanding the Scope of Immunotherapy in Colorectal Cancer: Current Clinical Approaches and Future Directions

Kreidieh

Mukherji

Temraz

et al. 2020

BioMed Research International

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The success of immune checkpoint inhibitors (ICIs) in an increasing range of heavily mutated tumor types such as melanoma has culminated in their exploration in different subsets of patients with metastatic colorectal cancer (mCRC). As a result of their dramatic and durable response rates in patients with chemorefractory, mismatch repair-deficient-microsatellite instability-high (dMMR-MSI-H) mCRC, ICIs have become potential alternatives to classical systemic therapies. The anti-programmed death-1 (PD-1) agents, Pembrolizumab and Nivolumab, have been granted FDA approval for this subset of patients. Unfortunately, however, not all CRC cases with the dMMR-MSI-H phenotype respond well to ICIs, and ongoing studies are currently exploring biomarkers that can predict good response to them. Another challenge lies in developing novel treatment strategies for the subset of patients with the mismatch repair-proficient-microsatellite instability-low (pMMR-MSI-L) phenotype that comprises 95% of all mCRC cases in whom treatment with currently approved ICIs has been largely unsuccessful. Approaches aiming at overcoming the resistance of tumors in this subset of patients are being developed including combining different checkpoint inhibitors with either chemotherapy, anti-angiogenic agents, cancer vaccines, adoptive cell transfer (ACT), or bispecific T-cell (BTC) antibodies. This review describes the rationale behind using immunotherapeutics in CRC. It sheds light on the progress made in the use of immunotherapy in the treatment of patients with dMMR-MSI-H CRC. It also discusses emerging approaches and proposes potential strategies for targeting the immune microenvironment in patients with pMMR-MSI-L CRC tumors in an attempt to complement immune checkpoint inhibition.

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A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal Cancer Models

Cited by 28 publications

References 55 publications

RETRACTED: The Oncolytic Virus in Cancer Diagnosis and Treatment

RETRACTED: The Oncolytic Virus in Cancer Diagnosis and Treatment

Gene-based Interventions for Cancer Immunotherapy

Expanding the Scope of Immunotherapy in Colorectal Cancer: Current Clinical Approaches and Future Directions

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