Vectors For Cancer Therapy Research Articles

Mesenchymal stem cells: a delivery vehicle for cancer therapy

Stem cells possess unlimited self-renewal properties and the ability to produce multiple differentiation progenitors.Mesenchymal stem cells(MSCs) can specifically migrate to multiple kinds of tumors and their metastases in a systemic manner(to all parts of the body).Therefore genetically modified MSCs can serve as vehicle of anticancer factors to inhibit growth of tumor.But many questions remain to be answered and the precise mechanisms remain unclear.This paper reviews the mechanism of MSC homing,MSCs as delivery vectors for cancer therapy and its advantages over traditional drug vehicle.MSCs as delivery vectors can be used for cellular therapy in future cancer treatment.

An adenoviral vector expressing human adenovirus 5 and 3 fiber proteins for targeting heterogeneous cell populations

Human adenovirus serotype 5 (HAdV-5) attaches to its primary receptor, the coxsackie and adenovirus receptor (CAR) as the first step of infection. However, CAR expression decreases as tumors progress, thereby diminishing the utility of HAdV-5-based vectors for cancer therapy. In contrast, many aggressive tumor cells highly express CD46, a cellular receptor for HAdV-3. We hypothesized that a mosaic HAdV vector, containing two kinds of fiber proteins, would provide extensive transduction in a heterogeneous population of tumor cells with varying expression levels of HAdV receptors. We therefore generated a fiber-mosaic HAdV vector displaying both a chimeric HAdV-3 fiber and the HAdV-5 fiber protein. We verified the structural integrity of purified viral particles and confirmed that the fiber-mosaic HAdV vector has expanded tropism. We conclude that the use of fiber-mosaic HAdV vectors is a promising approach for transducing a heterogeneous cell population with different expression levels of adenovirus receptors.

Non‐viral vectors for cancer therapy

Cancers are diverse and often resistant to therapeutic strategies. Gene therapy has yet to meet the promise of a breakthrough in cancer therapy. There are several barriers to overcome in cancer gene therapy. One of the biggest challenges is the design of appropriate vectors. Numerous viral and non-viral methods for gene transfer have been developed for human gene therapy, but both viral and non-viral vectors have limitations and advantages. In this review article, recent improvements in the development of non-viral vectors for delivering gene therapy for the treatment of cancer will be discussed.

75. Molecular Imaging of an EGFP-DRD2-Expressing Vaccinia Virus

Background: As oncolytic vectors for cancer therapy come to clinical trials, noninvasive monitoring of vector biodistribution will be necessary. Oncolytic vaccinia viruses (rVV) preferentially target, infect and replicate in tumours, leading to an amplification of expressed genes, and ultimately protein products, which can be targets for imaging. The creation of a vaccinia virus vector which will both treat tumours and allow non-invasive imaging is a novel and exciting concept. Purpose: To develop non-invasive strategies of monitoring rVV in vivo and to investigate the sensitivity of imaging, earliest time point and persistence of gene expression. Methods: Athymic mice were inoculated subcutaneously with 105 murine colon cancer cells (MC-38). Upon tumor formation (5–7 mm), increasing doses of vvDD-EGFP-DRD2 were injected intraperitoneally. Six days later, mice were anesthetized and imaged. To determine the earliest time-point of EGFP detection and persistence, mice implanted with tumors and injected with virus were imaged 48 hours post-injection of the virus and then every 24 hours thereafter until fluorescence of protein products (EGFP) completely dissipated (optical imaging). In vitro binding studies were done to confirm that the radioligand 123I[IBF] specifically binds tumour cells infected with the DRD2-expressing virus. In vivo studies are currently being performed to examine biodistribution and specificity of the 123I[IBF] in nude mice after delivery of vvDD-EGFP-DRD2. Results: EGFP expression intensified with increasing viral dose to a mean maximum intensity of 63 52 units/cm2 of tumour area (at 109 pfu). Interestingly, fluorescence intensity varied inversely with tumour size. Mice injected with a control virus showed no fluorescence. Gene expression was detected as early as 48 hrs post viral injection, peaked at 9d and slowly dissipated by day 30. Physical tumour size was measured and correlated with the intensity of gene expression. In vitro binding studies confirmed that the virally-expressed DRD2 receptor has a high affinity for 123I[IBF], and in vivo studies are on-going. Conclusions: Optical and nuclear imaging of rVV expressing EGFP and DRD2 provides a non-invasive assessment of vector biodistribution and persistence, and potentially will be able to image tumour responses. Thus, we feel oncolytic vaccinia virus is a promising vector for cancer therapy.