| First Author | Ross SL | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0183390 |
| PubMed ID | 28837681 | Mgi Jnum | J:247357 |
| Mgi Id | MGI:5914806 | Doi | 10.1371/journal.pone.0183390 |
| Citation | Ross SL, et al. (2017) Bispecific T cell engager (BiTE(R)) antibody constructs can mediate bystander tumor cell killing. PLoS One 12(8):e0183390 |
| abstractText | For targets that are homogenously expressed, such as CD19 on cells of the B lymphocyte lineage, immunotherapies can be highly effective. Targeting CD19 with blinatumomab, a CD19/CD3 bispecific antibody construct (BiTE(R)), or with chimeric antigen receptor T cells (CAR-T) has shown great promise for treating certain CD19-positive hematological malignancies. In contrast, solid tumors with heterogeneous expression of the tumor-associated antigen (TAA) may present a challenge for targeted therapies. To prevent escape of TAA-negative cancer cells, immunotherapies with a local bystander effect would be beneficial. As a model to investigate BiTE(R)-mediated bystander killing in the solid tumor setting, we used epidermal growth factor receptor (EGFR) as a target. We measured lysis of EGFR-negative populations in vitro and in vivo when co-cultured with EGFR-positive cells, human T cells and an EGFR/CD3 BiTE(R) antibody construct. Bystander EGFR-negative cells were efficiently lysed by BiTE(R)-activated T cells only when proximal to EGFR-positive cells. Our mechanistic analysis suggests that cytokines released by BiTE(R)-activated T-cells induced upregulation of ICAM-1 and FAS on EGFR-negative bystander cells, contributing to T cell-induced bystander cell lysis. |
