The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer
Open accessAbstract
Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602). Introducing the CAR construct via mRNA ensured safety by limiting the nontumor cell effects (on-target/off-tumor) of targeting c-Met. Patients with metastatic breast cancer with accessible cutaneous or lymph node metastases received a single intratumoral injection of 3 × 107 or 3 × 108 cells. CAR T mRNA was detectable in peripheral blood and in the injected tumor tissues after intratumoral injection in 2 and 4 patients, respectively. mRNA c-Met-CAR T cell injections were well tolerated, as none of the patients had study drug–related adverse effects greater than grade 1. Tumors treated with intratumoral injected mRNA c-Met-CAR T cells were excised and analyzed by immunohistochemistry, revealing extensive tumor necrosis at the injection site, cellular debris, loss of c-Met immunoreactivity, all surrounded by macrophages at the leading edges and within necrotic zones. We conclude that intratumoral injections of mRNA c-Met-CAR T cells are well tolerated and evoke an inflammatory response within tumors. Cancer Immunol Res; 5(12); 1152–61. ©2017 AACR.
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Cites
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Self-citationEfficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
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Self-citationmRNA-based therapeutics: powerful and versatile tools to combat diseases
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Clinical lessons learned from the first leg of the CAR T cell journey
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Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours
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Metadata
- Authors
- Tchou, J., Zhao, Y., Levine, B. L., Zhang, P. J., Davis, M. M., Melenhorst, J. J., Kulikovskaya, I., Brennan, A. L., Liu, X., Lacey, S. F., Posey, A. D., Williams, A. D., So, A., Conejo-Garcia, J. R., Plesa, G., Young, R. M., McGettigan, S., Campbell, J., Pierce, R. H., Matro, J. M., DeMichele, A. M., Clark, A. S., Cooper, L. J., Schuchter, L. M., Vonderheide, R. H., & June, C. H.
- Venue
- Cancer Immunology Research
- Published
- 2017-11-30
- Volume
- 5
- Issue
- 12
- Pages
- 1152-1161
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- OpenAlex
- W2768089870
- Cited by
- 452
- References
- 26
- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- green
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- Tchou, J., Zhao, Y., Levine, B. L., Zhang, P. J., Davis, M. M., Melenhorst, J. J., Kulikovskaya, I., Brennan, A. L., Liu, X., Lacey, S. F., Posey, A. D., Williams, A. D., So, A., Conejo-Garcia, J. R., Plesa, G., Young, R. M., McGettigan, S., Campbell, J., Pierce, R. H., . . . June, C. H. (2017). Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.cir-17-0189
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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