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Consideration with “Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with DDMC non-viral vector–p53”

A Baliaka et al. has reported below: “Lung cancer has not yet been resolved by new treatments. New topical targeting is a way to enhance treatment and reduce side effects. Intratumoral gene therapy is a method of topical treatment that can be used either in early-stage lung cancer before surgery or in advanced stages as palliative care. There is also an increasing demand for efficient gene transfection to target local cancer tissues using novel non-viral vectors while at the same time protecting normal tissues. In this study, C57BL/6 mice inoculated with the LL/2 cell line were divided into three groups: (a) control, (b) intravenous, and (c) intratumoral gene therapy. The novel 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector (DDMC) (Ryujyu Science Corporation) was the first to conjugated to Addgene’s plasmid pSicop53. The purpose of this study was to evaluate the safety and efficacy of targeted gene therapy in the Lewis lung cancer model. Indeed, different dosing regimens have different pharmacokinetics, but intratumoral administration has shown increased survival and decreased distant metastases. Intratumoral gene therapy can be considered as an efficient topical treatment for lung cancer. The average survival rate was expressed as follows from the viewpoint of efficiency: intratumor (17.4 days)> intravenous (12.6 days)> control (12.6 days).”

However, in the table of mice survival by A Baliaka et al. [1], Smirnov-Grubbs test [2] are done for Outlier detected a normal distribution as shown in Table 1. In this paper, it may be better to delete 4 samples of 3 and 7 survival days of both control and intravenous, statistically.

Table 1 Statistical evaluation of outliers in data analysis (Smirnov-Grubbs test).

The ANOVA-Test for three groups are also done as Table 2, and good results are obtained (P < 0.05). The mean survival should be displayed as intratumoral (17.3 days)> intravenous(15.6 days)>control(13.2 days) after correction.

Table 2 ANOVA.

It may be depended on rapid intravenous injection that four mice died earlier after administration containing control. It is difficult for the viral vectors to select multiple-dose because of neutralized antibody with its immunogenicity such as AAV vector. The lipofection reagents are also not suitable to transfect in-vivo for its unstable properties.

Results show that the complexes by DDMC/p53 have an excellent anticancer activity for systemic administration by depending on EPR effect [3] and avoidance of RES [4, 5].

Polymer-based drug delivery systems (DDS) are widely used as carriers for targeted drug delivery due to promoting EPR effect and avoidance of RES.

DDS technology by transfection reagents (DDMC) [6] in vivo compose of

  1. 1.

    A long retention time in body by control of renal excretion.

  2. 2.

    An antigenicity reducing by reticuloendothelial system (RES).

  3. 3.

    A high protect facility for DNase or RNase degradation.

  4. 4.

    A drug to a target effectively by the enhanced permeation and retention (EPR) effect.

DDMC will become the most important DDS technology after the COVID-19 pandemic.

References

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YO, PZ, RJ, MO, NK, and YE designed research. YO, PZ, RJ, MO, NK, and YE performed research. YO, PZ, RJ, MO, and YE analyzed the data. YO, PZ, RJ, MO, and YE wrote the paper.

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Correspondence to Y. Onishi.

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Onishi, Y., Zarogoulidis, P., Ji, RC. et al. Consideration with “Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with DDMC non-viral vector–p53”. Gene Ther (2021). https://doi.org/10.1038/s41434-021-00298-y

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