Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope

Abstract

Cancer is among the leading causes of death worldwide. Therefore, improving cancer therapeutic strategies using novel alternatives is a top priority on the contemporary scientific agenda. An example of such strategies is immunotherapy, which is based on teaching the immune system to recognize, attack, and kill malignant cancer cells. Several types of immunotherapies are currently used to treat cancer, including adoptive cell therapy (ACT). Chimeric Antigen Receptors therapy (CAR therapy) is a kind of ATC where autologous T cells are genetically engineered to express CARs (CAR-T cells) to specifically kill the tumor cells. CAR-T cell therapy is an opportunity to treat patients that have not responded to other first-line cancer treatments. Nowadays, this type of therapy still has many challenges to overcome to be considered as a first-line clinical treatment. This emerging technology is still classified as an advanced therapy from the pharmaceutical point of view, hence, for it to be applied it must firstly meet certain requirements demanded by the authority. For this reason, the aim of this review is to present a global vision of different immunotherapies and focus on CAR-T cell technology analyzing its elements, its history, and its challenges. Furthermore, analyzing the opportunity areas for CAR-T technology to become an affordable treatment modality taking the basic, clinical, and practical aspects into consideration.

Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma

“…Burkitt lymphoma has similarities to both leukemia and solid tumors. Therapeutic failure in some patients may be partly attributable to the limited increase in CAR T cell levels induced by complex and heterogeneous TIME ( 32 ). In our study, three partially responsive patients eventually experienced disease progression and died.…”

Recent advances and clinical pharmacology aspects of Chimeric Antigen Receptor (CAR) T‐cellular therapy development

“…[11][12][13] Although protocols for manufacturing clinical grade CAR-T cells have been well-established, a number of manufacturing and regulatory challenges, such as processing techniques, quality control mechanisms, logistic developments, and financial liabilities need to be addressed to develop robust CAR-T cell therapies for the patients. 11,14…”

“…Once isolated, autologous T cells undergo ex vivo enrichment and activation, followed by the transduction of the CAR cDNA via gene expression vectors, such as retroviral and lentiviral vectors. The genetically engineered T cells are expanded in large scale, washed, concentrated, and cryopreserved, then infused back to the patient for treatment 11–13 . Although protocols for manufacturing clinical grade CAR‐T cells have been well‐established, a number of manufacturing and regulatory challenges, such as processing techniques, quality control mechanisms, logistic developments, and financial liabilities need to be addressed to develop robust CAR‐T cell therapies for the patients 11,14 …”

Glycoconjugate Nanoparticle-Based Systems in Cancer Immunotherapy: Novel Designs and Recent Updates

“…Subsequent work on Point #2 above led to the discovery that, engineering a patient’s own T-cells with a binding molecule (antibody fragments such as an ScFv) to a tumor-specific antigen (a so-called neoantigen) and linking this to signaling domains that promote T-cell proliferation after neoantigen engagement, could eliminate certain tumors. The ScFv portion denoted as a Chimeric Antigen Receptor (CAR) spawned an entire new field of study and the development of many new therapies called CAR-T cells ( 7 , 50 ). These can be specifically tailored to mutated or overexpressed antigens on a tumor and have, to date, been highly successful against particular subsets of tumors, especially lymphomas.…”