Next-generation CAR T cells to overcome current drawbacks.
Stefan LundhSayantan MajiJan Joseph MelenhorstPublished in: International journal of hematology (2020)
As a rapidly emerging treatment in the oncology field, adoptive transfer of autologous, genetically modified chimeric antigen receptor (CAR) T cells has shown striking efficacy and is curative in certain relapsed/refractory patients with hematologic malignancy. This treatment modality of using a "living drug" offers many tantalizing and novel therapeutic strategies for cancer patients whose remaining treatment options may have otherwise been limited. Despite the early success of CAR T cells in hematologic malignancies, many barriers remain for widespread adoption. General barriers include cellular manufacturing limitations, baseline quality of the T cells, adverse events post-infusion such as cytokine release syndrome (CRS) and neurotoxicity, and host rejection of non-human CARs. Additionally, each hematologic disease presents unique mechanisms of relapse which have to be addressed in future clinical trials if we are to augment the efficacy of CAR T treatment. In this review, we will describe current barriers to hindering efficacy of CAR T-cell treatment for hematologic malignancies in a disease-specific manner and review recent innovations aimed at enhancing the potency and applicability of CAR T cells, with the overall goal of building a framework to begin incorporating this form of therapy into the standard medical management of blood cancers.
Keyphrases
- clinical trial
- healthcare
- cell therapy
- stem cells
- acute lymphoblastic leukemia
- cell proliferation
- oxidative stress
- combination therapy
- induced apoptosis
- young adults
- open label
- diffuse large b cell lymphoma
- prognostic factors
- replacement therapy
- smoking cessation
- endoplasmic reticulum stress
- electronic health record
- adverse drug
- phase ii