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Figures S1 - S5 from Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer

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posted on 2023-04-03, 23:04 authored by Julia Tchou, Yangbing Zhao, Bruce L. Levine, Paul J Zhang, Megan M. Davis, Jan Joseph Melenhorst, Irina Kulikovskaya, Andrea L Brennan, Xiaojun Liu, Simon F. Lacey, Avery D. Posey, Austin D. Williams, Alycia So, Jose R. Conejo-Garcia, Gabriela Plesa, Regina M. Young, Shannon McGettigan, Jean Campbell, Robert H. Pierce, Jennifer M. Matro, Angela M. DeMichele, Amy S. Clark, Laurence J. Cooper, Lynn M. Schuchter, Robert H. Vonderheide, Carl H. June

S1. Clinical trial schema. S2. Representative immunohistochemistry (IHC). S3. Histology and IHC of tumor tissue pre and post intratumoral injection of RNA CAR T c- Met from one patient. S4. Histology and IHC of tumor tissue pre and post intratumoral injection with lidocaine (1 mL) and RNA CAR T c-Met (1 mL) from another patient. S5. Characterization of CD68+ tumor infiltrated immune cells using multiplex IHC analyses as described (1) in pre and post IT injection of RNA CAR T c-Met tumor tissue sections from two patients.

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NCI

Breast Cancer Alliance

Breast Cancer Research Foundation

Pennsylvania Department of Health

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ARTICLE ABSTRACT

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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    Cancer Immunology Research

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    Breast CancerImmunotherapyCellular immunotherapy

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