CAR-T cell Therapy

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CAR-T cell Therapy

Chimeric antigen receptor T cells are T cells with genetic engineering to produce an artificial T cell receptor for use in immunotherapy.

Therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal.

Nowicki KW, D’Angelo MP, Sekula RF Jr. Engineering Chimeric Antigen Receptors Into Homing Missiles. Neurosurgery. 2018 Dec 27. doi: 10.1093/neuros/nyy629. [Epub ahead of print] PubMed PMID: 30590676 1).

CAR T cells were originally developed by Kochenderfer et al. against leukemia and lymphoma but have been adapted and explored as immunotherapy against central nervous system tumors. CAR T cells are synthetically engineered from a patient’s autologous T-cells to recognize cancer-specific antigens and generate a strong anti-tumor immune response 2).

Chimeric antigen receptor T cell for solid tumors

Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment 3)

CAR-modified T cells can mediate long-term durable remissions in B cell malignancies, but expanding this platform to solid tumors requires the discovery of surface targets with limited expression in normal tissues.

CAR therapy has shown promise in treating cancer, but at the cost of unexpected toxicity against normal tissues, not predicted by preclinical testing. Johnson et al. are working to generate more physiologically relevant models for preclinical CAR toxicity testing, and in doing so, have discovered that CAR therapy induces immunogenic cell death, with the potential for cures 4).

see EGFRvIII targeted chimeric antigen receptor T.

Chimeric antigen receptor T cell for glioblastoma

Chimeric antigen receptor T cell for glioblastoma

1)

Nowicki KW, D’Angelo MP, Sekula RF Jr. Engineering Chimeric Antigen Receptors Into Homing Missiles. Neurosurgery. 2018 Dec 27. doi: 10.1093/neuros/nyy629. [Epub ahead of print] PubMed PMID: 30590676.
2)

Kochenderfer JN, Wilson WH, Janik JE, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099-4102.
3)

Qu C, Zhang H, Cao H, Tang L, Mo H, Liu F, Zhang L, Yi Z, Long L, Yan L, Wang Z, Zhang N, Luo P, Zhang J, Liu Z, Ye W, Liu Z, Cheng Q. Tumor buster – where will the CAR-T cell therapy ‘missile’ go? Mol Cancer. 2022 Oct 19;21(1):201. doi: 10.1186/s12943-022-01669-8. PMID: 36261831.
4)

Johnson LA, Sanchez-Perez L, Suryadevara CM, Sampson JH. Chimeric antigen receptor engineered T cells can eliminate brain tumors and initiate long-term protection against recurrence. Oncoimmunology. 2014 Jul 3;3(7):e944059. eCollection 2014. PubMed PMID: 25610729; PubMed Central PMCID: PMC4292711.

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