A Comprehensive Review of Recent Advancements in Cancer Immunotherapy and Generation of CAR T Cell by CRISPR-Cas9

Abstract

The mechanisms involved in immune responses to cancer have been extensively studied for several decades, and considerable attention has been paid to harnessing the immune system’s therapeutic potential. Cancer immunotherapy has established itself as a promising new treatment option for a variety of cancer types. Various strategies including cancer vaccines, monoclonal antibodies (mAbs), adoptive T-cell cancer therapy and CAR T-cell therapy have gained prominence through immunotherapy. However, the full potential of cancer immunotherapy remains to be accomplished. In spite of having startling aspects, cancer immunotherapies have some difficulties including the inability to effectively target cancer antigens and the abnormalities in patients’ responses. With the advancement in technology, this system has changed the genome-based immunotherapy process in the human body including the generation of engineered T cells. Due to its high specificity, CRISPR-Cas9 has become a simple and flexible genome editing tool to target nearly any genomic locus. Recently, the CD19-mediated CAR T-cell (chimeric antigen receptor T cell) therapy has opened a new avenue for the treatment of human cancer, though low efficiency is a major drawback of this process. Thus, increasing the efficiency of the CAR T cell (engineered T cells that induce the chimeric antigen receptor) by using CRISPR-Cas9 technology could be a better weapon to fight against cancer. In this review, we have broadly focused on recent immunotherapeutic techniques against cancer and the use of CRISPR-Cas9 technology for the modification of the T cell, which can specifically recognize cancer cells and be used as immune-therapeutics against cancer.

Immunotherapy for Prostate Cancer: A Current Systematic Review and Patient Centric Perspectives

“…However, a common adverse event is cytokine storm syndrome, which is the double-edged sword of immunotherapeutic treatment [ 90 , 91 , 92 ]. Newer formulations of molecules with lower affinity for CD3 may help in overcoming the cytokine storm among patients [ 93 , 94 ].…”

Molecular and therapeutic effect of CRISPR in treating cancer

“…First clinical trial of CRISPR/Cas 9 mediated PD1 knockout T cell therapy was done for lung cancer by interfering with the normal immune response of PD1 which takes advantage in cancer to proliferate [ 42 ]. Taken together there are several researches on CRISPR/Cas9-PD1 tumor-infiltrating lymphocytes (TIL) based adoptive T cell therapy (ACT) [ 43 , 44 ] by blocking the checkpoint to restore the T cell exhaustion [ 45 ] PD-1/PD-1L1 related therapies for tumor immunity [ 46 ] demonstrate the effect of CRISPR/Cas9 in tumor therapy. By using Cas9 to disrupt CAR T cells, immune checkpoints such as PD-1 could overcome the major challenge of checkpoint inhibition in tumor cells [ 47 ] To reduce the alloreactivity, multiplex CRISPR CAR T cells being used as an anti-tumor agent by blocking PD1 inhibitory pathway with excision of TCR, B2M, and PD1 in T cells as a potential leukemic tumor treating model.…”

Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus

“…Finding a ligand that delivers a specifc signaling profle and binding to the target is a common goal of drug development. Tis is true, in particular for signaling receptors [39,40]. It is possible to use a full agonist, which vigorously stimulates the signaling and activation of the receptor, a partial agonist, which revitalizes signaling only slightly, and a neutral antagonist [41,42], which inhibits the body's natural agonists from binding but does not signal on its own, or an inverse agonist, which decreases signaling below basal levels [43,44].…”