Immunotherapy for treating metastatic colorectal cancer

Boghossian, Shahe; Robinson, Stuart; Delwig, Alexei von; Manas, Derek; White, Steve

doi:10.1016/j.suronc.2010.10.004

Cited by 11 publications

(5 citation statements)

References 102 publications

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“…Immunotherapy-based therapies have the potential to activate a tumour antigen-specific response, which can help to eradicate the tumour and reduce the risk of disease recurrence. 6 , 7 , 8 , 9 Delivering immunotherapies clinically can be achieved through a number of approaches including the use of gene therapy, which has many applications and methodologies already developed for cancer treatment. 10 , 11 , 12 , 13 For gene therapy to be successful, safe and efficient gene delivery is critical.…”

Section: Introductionmentioning

confidence: 99%

Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models

et al. 2014

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Antitumour efficacy of electroporated pEEV, coding for granulocyte–macrophage colony-stimulating factor and the B7-1 costimulatory immune molecule (pEEVGmCSF-b7.1) in growing solid tumours, was investigated and compared with a standard plasmid. Application of pEEVGmCSF-b7.1 led to complete tumour regression in 66% of CT26-treated tumours and 100% in the B16F10-treated tumours at day 150 post-treatment. pEEVGmCSF-b7.1 treatment was found to significantly enhance levels of both innate and adaptive immune populations in tumour and systemic sites, which corresponded to significantly increased tissue levels of proinflammatory cytokines including interferon-γ (IFN-γ) and interleukin-12 (IL-12). In contrast, pEEVGmCSF-b7.1 treatment significantly reduced the T-regulatory populations and also the anti-inflammatory cytokine IL-10. Upon further characterisation of functional immune responses, we observed a significant increase in cytotoxic (CD107a+) and IFN-γ-producing natural killer cells and also significantly more in IL-12-producing B cells. Importantly, splenocytes isolated from pEEVGmCSF-b7.1-treated ‘cured' mice were tumour-specific and afforded significant protection in a tumour rechallenge model (Winn assay). Our data indicate that electroimmunogene therapy with the non-viral pEEVGmCSF-b7.1 is able to induce potent and durable antitumour immune responses that significantly reduce primary and also secondary tumour growth, and thus represents a solid therapeutic platform for pursuing future clinical trials.

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Section: Introductionmentioning

confidence: 99%

Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models

et al. 2014

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“…Radiotherapy is commonly given as adjuvant treatment for tumours within the rectum. Although biological agents are used for selected patients with advanced disease, immunotherapy is not as commonly utilised for the treatment of CRC [1][2][3][4][5][6]. However, recent advances in our understanding of tumour immunology have reignited interest in such therapeutic strategies across a range of tumour types [7][8][9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Cancer/Testis Antigens and Colorectal Cancer, gene expression,

Sammut¹,

Ja²

2013

J Genet Syndr Gene Ther

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Some antigenic proteins are only normally present in male gametogenic tissues in the testis and not in normal somatic cells. When the genes that encode these proteins are expressed in cancerous cells they are referred to as cancer/testis antigen (CTA) genes. Some CTA genes have been proven to encode immunogenic proteins that have been used as successful immunotherapy targets for various forms of cancer. Thus, there has been a focus over the past two decades to characterise their potential applications for the treatment and/or diagnosis of cancer. Colorectal cancer is among the most common forms of cancer and a leading cause of cancer related death worldwide. It is generally regarded as having low levels of CTA gene expression, compared to some other cancers such as malignant melanoma. There is now scope to revisit this dogma, as an ill-defined cohort of colorectal cancers do exhibit CTA gene expression, potentially exposing these tumours to CTA-based therapeutic and/or diagnostic strategies as they are developed.

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“…The immunogenic character of MSI-H and MAP carcinomas remains to be fully exploited and might hold a promising source of therapeutic opportunities. Vaccination and T cellbased immunotherapeutic approaches provide a way to prolong survival of certain groups of patients in clinical trials but treatment of advanced disease still remains a promise (114). This may be explained 2-fold: as demonstrated, advanced CRCs already acquired immune-evasive phenotypes and are therefore insensitive to therapeutic vectors that require antigen recognition, and the intrinsic nature of the clinical trials does not allow the selection of patients with cancers that present immunogenic features.…”

Section: Management Of Msi-h and Map Crc Patientsmentioning

confidence: 99%

Role of the microenvironment in the tumourigenesis of microsatellite unstable and MUTYH-associated polyposis colorectal cancers

Miranda

Hes

Wezel³

et al. 2012

Mutagenesis

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Two forms of genomic instability can be distinguished in colorectal cancer (CRC) tumourigenesis. One is characterised by pronounced chromosomal instability (CIN), while the other relates to alterations produced at the nucleotide level that preferentially target microsatellite sequences. Tumours developing under the latter form of genomic instability possess a microsatellite instability-high (MSI-H) phenotype due to inactivation of the DNA mismatch repair system. The most recently described CRC syndrome, MUTYH-associated polyposis (MAP), shares characteristics with both MSI-H and CIN cancers. MAP carcinomas develop from the impairment of the base excision repair system, where MUTYH is involved, but also present a peculiar form of CIN. Several clinicopathological characteristics of MSI-H and MAP CRCs overlap such as tumour location, clinical prognosis and histological features. We propose that MSI-H and MAP CRCs are particularly prone to interact with their tumour microenvironment. A great deal of this interaction is probably stimulated by the immunogenic character of those tumours, known to possess a high mutagenic potential. The accumulation of mutations in coding regions of the genome of MSI-H and MAP carcinomas is likely to translate into a surplus of neo-antigens that trigger an anti-tumour immune response. The immune system constitutes thus an important vector of selective pressure that favours the outgrowth of tumour clones with immune-evasive phenotypes. In this review, we summarise the evidence for the influence of the tumour microenvironment in MSI-H and MAP tumourigenesis. Furthermore, we discuss how particular features of MSI-H and MAP CRCs can be exploited for the development of therapeutic strategies for affected patients.

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Immunotherapy for treating metastatic colorectal cancer

Cited by 11 publications

References 102 publications

Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models

Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon adenocarcinoma and melanoma cancer models

Cancer/Testis Antigens and Colorectal Cancer, gene expression,

Role of the microenvironment in the tumourigenesis of microsatellite unstable and MUTYH-associated polyposis colorectal cancers

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