Abstract
Despite significant advancements, relapses, and persistent malignancies are still a major challenge faced by the oncologists. Immunotherapy has shown remarkable potential in induction of sustained remission in refractory malignancies. Chimeric antigen receptor T-cell (CAR-T) therapy is a newer treatment methodology approved by the Food and Drug Administration (FDA). The chimeric pairing of an antigen receptor with the T-cell receptor (TCR) intracellular signaling domain allows cluster of designation 8 (CD8) cytotoxic T-cells to target cell surface makers independent of major histocompatibility complex (MHC) activation. Another essential feature which contributes to the broad applicability of CARs and expanding their potential targets is their ability to bind not only to proteins but also to carbohydrate and glycolipid structures. Their antigen-specific and targeted immune responses have shown promising outcomes in clinical trials particularly involving B-cell malignancies and solid tumors. High remission rates and low percentages of relapses have caused a paradigm shift in the treatment of relapsed or refractory cancers. Challenges include side effects such as cytokine release syndrome, on-target off-tumor toxicities, and replication of its success in treating solid tumors. The burden of side effects and hefty cost of treatment are major obstacles which could hinder its progress globally. Nevertheless, ongoing research would only result in a maximized therapeutic potential in addition to more patient- and cost-friendly treatment. In this review, we aim to provide the readers an overview of chimeric antigen receptor T-cell therapy, a relatively new advancement in the world of immuno-oncology and thereby also discussing its advantages, side effects and future challenges.
Highlights
BackgroundConventionally, radiotherapy, and chemotherapy have been employed in the treatment of cancer for decades
In the 1980s, Rosenberg and colleagues were first to show the potential of immunotherapy in treating malignancies by employing lymphokine-activated killer cells (LAK) produced by taking blood from the patients and treating their lymphocytes with interleukin 2 (IL-2) [1]
As far as the challenges are concerned, the foremost challenge faced by the oncologists is lack of a uniform and standard dose of transfusion cells
Summary
Radiotherapy, and chemotherapy have been employed in the treatment of cancer for decades. Decades of hard work has come into fruition by the development of CARs, where each CAR T cell can kill numerous tumor cells by antigen release and promote the tumor lymphocytes to kill cancer cells These engineered T cells are a new group of therapeutic agents which are ready to penetrate the saturated field of oncology as a ray of hope, especially in leukemias and lymphomas. A ligand for a cell-surface molecule consisting of a single-chain variable fragment (scFv) derived from a monoclonal antibody or an antigen-binding fragment (Fab) joined by a flexible linker to signal domains assembled to redirect T-cell function [6] It determines receptor selectivity and affinity and is similar to the light chain region of an antibody
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