Modified T-cells (using TCR and CTAs)‎, chimeric antigen receptor (CAR)‎ and other molecular tools in recent gene therapy

الملخص EN

T-cell-based cancer immunotherapy by the transfer of cloned TCRs that are isolated from tumor penetrating T-cells becomes a possibility through NY-ESOc259; a human-derived affinity-enhanced TCR that provides a level of sufficiency in long-term safety and efficacy.

NY-ESOc259 recognizes a peptide common to CTAs (LAGE-1 and NY-ESO-1) in melanoma.

Risks associated with insertion related transformation in gene therapy have been alleviated through strategies that include the engineering of transcription activator like effector nucleases (TALEN), RNA-guided nucleases (CRISPR/Cas9), Zinc-finger nucleases (ZFN).

Cancer immunotherapy based on the genetic modification of autologous T-cells (dependent on the engineered autologous CD8+ T-cells), designed to distinguish and destroy cells bearing tumor-specific antigens via a CAR is able to exterminate B-cell leukemias and lymphomas that are resilient to conventional therapies.

A tool with a very large reservoir of potentials in molecular therapy strategy is the Pluripotent Stem Cells (PSC), with pluripotency factors that include Klf4, Sox2, c-Myc, Oct4, differentiating into disease-associated cell phenotypes of three germ layers, comprising of mesoderm (e.g.

cardiac cells, blood and muscle), endoderm (liver, pancreas) and ectoderm (epidermis, neurons).

It finds good application in disease modelling as well as therapeutic options in the restoration of CGD by using AAVS1 as the vector where the therapeutic cassette is integrated into the locus to restore superoxide production in the granulocytes.

Fascinatingly, Clinical trial involving iPSC are already underway where scientists have plans to use iPSC-derived cells to treat macular degeneration (a devastating age-related eye disease).

Application of these findings has redefined incurable diseases disorders as curable.