Researchers Highlight Administration of CAR T-Cell Therapy Using Modified AAV

In a preclinical study, the researchers were able to show that their modified adeno-associated virus (AAV) vector safely delivered the chimeric antigen receptor (CAR) gene into host cells and produced enough CAR T cells to cause effective tumor regression and induce anti-tumor immunological reactions. characteristics in a mouse model of human T cell leukemia.

Newly published findings document a new approach that researchers believe could make chimeric antigen receptor (CAR) T cell therapy for leukemia simpler and less expensive because it does not require patient lymphodepletion or processes. β of the current production of CAR T cells. The approach allows the patient to generate CAR T cells by injecting an adeno-associated virus (AAV) vector which provides the CAR gene.

In the present study, the researchers were able to show that their modified AAV vector safely delivered the AUTO in host cells and produced enough CAR T cells to induce efficient tumor regression and induce antitumor immunological features in a mouse model of human T cell leukemia. Notably, this response was observed after a single infusion and CAR cells T generated circulated in the host body for weeks, able to detect and attack target cells.

“To our knowledge, this is the first report describing that an AAV carrying a CAR gene can reprogram immune cells in vivo to generate enough CAR T cells to induce tumor regression,” the researchers said. “Our current strategy of AAV carrying the CAR gene contrasts with the costly and time-consuming method of conventional manufacture of CAR T therapy, which requires the isolation of primary T cells and the introduction and expansion of the transgene via lentiviral vectors. or ex vivo retroviral vectors. “

According to the researchers, AAV is a popular and widely studied method for delivering therapeutic genes, often used to transport genetic material into target cells in order to cure or treat disease.

For the study, the researchers chose CAR targeting CD4 because of the aggressive nature of CD4 + leukemia and lymphoma, which often do not respond to chemotherapy.

“The first preclinical studies of CAR T cells to target CD4 + tumors are encouraging, but to date no standard care has been developed,” the group explained. “In addition, CD4 + cells are the main latent reservoir of HIV, which poses a challenge for HIV eradication; therapies targeting CD4 + cells can also be translated into treatment for HIV and treatments for other infectious diseases, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and psoriasis.

The researchers noted that there was complete depletion of CD4 + in mice, raising concerns about possible long-term or clinical effects, as long-term depletion of CD4 helper T cells can cause “on the target, excluding tumor ”toxicities and immunodeficiency.


Nawaz W, Huang B, Xu S, et al. AAV-mediated in vivo CAR gene therapy for targeting human T cell leukemia. Blood cancer J. 2021; 11 (6): 119. doi: 10.1038 / s41408-021-00508-1

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