Reprogramming T Cells: CAR-T Cell Therapy

As more is learned about the immune system, many immunotherapies are being developed which utilize inducing the immune system to function in a different way, whether it be boosting the immune system or directly targeting the diseased cells. The defense system humans have is great and all, but cancer likes to weaken the immune system and use it to its advantage by reducing the ability to identify abnormal cancer cells, therefore increasing tumor survival (Mohanty et al., 2019). 

Chimeric antigen receptor T (CAR-T) cell therapy is a newer immunotherapeutic approach that treats hematological malignancies (Han et al., 2021). CAR-T cell therapy has shown promising results with approximately an 80% reduction in remission rates, particularly for acute lymphoblastic leukemia and non-Hodgkin lymphomas. This type of therapy can potentially offer a fast and safer treatment plan to treat non-solid and solid tumors, although how effective it is against solid tumors is still undetermined (Mohanty et al., 2019). In 2017, two kinds of CAR-T cell therapies were FDA approved: Kymriah and Yescarta. Then, in 2020, Tecartus was approved (Han et al., 2021). 

So, what’s so special about these CAR-T cells? CAR-T cells consist of two parts: T cells from the patients' blood and a genetically engineered CAR designed to target specific tumor antigens (Han et al., 2021 and Mohanty et al., 2019). Chimeric antigen receptors are expressed on the T cells once the cDNA is integrated into the target cells. The most traditional mode of delivery is through a lentiviral vector, which is derived from HIV-1, due to their efficient transduction and stable integration and expression into nondividing and dividing cells in vitro and in vivo (Mohanty et al., 2019). The amazing thing that the receptors do is directly identify the tumor antigen without the help of the major histocompatibility complex (MHC) (Han et al., 2021). When the receptors bind to that specific tumor antigen, it activates a signal, telling the T cell to do its job. Additionally, these cells remain stable for several years in the body as long-term memory cells which allows them to recognize and kill cancer cells in the case of relapse (Mohanty et al., 2019). 

Obviously, there are some challenges to CAR-T cell therapy. There’s potential for serious side effects like neurological toxicity, cytokine release syndrome, B cell aplasia, tumor lysis syndrome, and anaphylaxis (Mohanty et al., 2019). But, despite these reactions, there have been methods found that reduce cytotoxicity and increase the CAR-T cells’ curative effect (Han et al., 2021). It’s cool but also a little crazy that we can reprogram our immune cells and redirect them to target cancerous cells.

References:

Han, D., Xu, Z., Zhuang, Y., Ye, Z., & Qian, Q. (2021). Current Progress in CAR-T Cell Therapy for Hematological Malignancies. Journal of Cancer, 12(2), 326–334. https://doi.org/10.7150/jca.48976

Mohanty, R., Chowdhury, C.R., Arega, S., Sen, P., Ganguly, P., & Ganguly, N. (2019). CAR T cell therapy: A new era for cancer treatment (Review). Oncology Reports, 42, 2183-2195. https://doi.org/10.3892/or.2019.7335