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Development of Cell Penetrating Peptides for Effective Delivery of Recombinant Factors into Target Cells

Vijakumaran U, Nordin F, Hamid ZA, Abdullah M, Jun TG

Protein Pept Lett, 2020;27(11):1092-1101.
PMID: 32484079 DOI: 10.2174/0929866527666200525164135

The cell membrane is a protective layer that strictly controls the passage of molecules restricting the delivery of biomolecules such as drugs, oligonucleotides, peptides, and siRNA into the cells. This shortcoming has been overcome by the discovery of Cell-Penetrating Peptides (CPPs) that has undergone 30 years of evolution. To date, CPPs are largely modified to improve its efficacy and to suit the different delivery applications. The modes of CPPs penetration are still an unresolved mystery and requires further investigations to increase its effectiveness and to diversify its use. Despite having huge potential as a biomolecule carrier, CPPs also have some drawbacks. In this review, the natural and synthetic CPPs, the modifications that have been conducted on CPPs to improve its efficacy, its extended applications, modes of penetration and limitation as well as challenges will be discussed.
Antibody-Dependent Cell-Mediated Cytotoxicity Through Natural Killer (NK) Cells: Unlocking NK Cells for Future Immunotherapy

Chin DS, Lim CSY, Nordin F, Arifin N, Jun TG

Curr Pharm Biotechnol, 2022;23(4):552-578.
PMID: 34414871 DOI: 10.2174/1389201022666210820093608

BACKGROUND: Natural killer (NK) cells have potent effector functions that can be further improved for therapeutic purposes through antibody-dependent cell-mediated cytotoxicity (ADCC). Specific killing of virus-infected cells and cancer cells is modulated through target specific antibodies that subsequently recruit NK cells for ADCC. NK cells produce cytokines similar to activated T cells, but is less persistent as NK cells have short-lived responses. These features benefit the development of customisable and more individualised cell-based therapies.
OBJECTIVES: Preclinical studies with NK cells were promising and several clinical studies are ongoing to investigate their use in antibody therapies. However, more reliable ADCC assays are required for evaluating NK cell activity to optimise therapeutic antibodies. The therapeutic potential of NK cell therapy could then be improved by harnessing ADCC.
METHODS: This review discusses recent studies on key components of NK cell-mediated ADCC, current clinical trials involving NK cells, ADCC assay developments and various techniques to improve ADCC.
RESULTS: Improvements can be made to NK-mediated ADCC through modifications of antibodies, effector cells and target antigens. Different aspects of antibodies were studied extensively, including modifying glycosylation patterns, novel production methods, combination regiments, bispecific antibodies, and conjugated antibodies. Modification of NK cells and tumour surface markers could improve ADCC of even treatment-resistant cancer cells. Additives such as cytokines and other immunomodulatory agents can further augment ADCC to supplement NK cell-based therapies.
CONCLUSION: ADCC improvements could be incorporated with current biological techniques such as adoptive transfer of NK cells and chimeric antigen receptor (CAR) NK cells, to improve the outcome of NK cell-based therapy and pave the way for future immunotherapies.
Current Status of Training and Certification for Congenital Heart Surgery Around the World: Proceedings of the Meetings of the Global Council on Education for Congenital Heart Surgery of the World Society for Pediatric and Congenital Heart Surgery

Tchervenkov CI, Herbst C, Jacobs JP, Al-Halees Z, Edwin F, Dearani JA, et al.

World J Pediatr Congenit Heart Surg, 2021 05;12(3):394-405.
PMID: 33942697 DOI: 10.1177/21501351211003520

The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.

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