Targeting and suppression of HER3-positive breast cancer by T lymphocytes expressing a heregulin chimeric antigen receptor.

Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1ß (HRG1ß) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors. Our results showed that HRG1ß-CAR was successfully constructed, and T cells were transduced at a rate of 50%. The CAR-T cells specifically recognized and killed HER3-overexpressing breast cancer cells SK-BR-3 and BT-474 in vitro, and displayed potent tumoricidal effect on SK-BR-3 xenograft tumor models. Our results suggest that HRG1ß-based CAR-T cells effectively suppress breast cancer driven by HER family receptors, and may provide a novel strategy to overcome cancer resistance to HER2-targeted therapy.

Association between ABCB1 (3435C>T) polymorphism and susceptibility of colorectal cancer: A meta-analysis.

Studies on the relationship between ABCB1 3435C>T polymorphism (rs1045642) and colorectal cancer (CRC)susceptibility have yielded inconclusive results. To clarify this issue, we undertook a meta-analysis to investigate the relationship between rs1045642 and CRC risk.Three electronic scientific publication databases (Cochrane Library, Pubmed, Embase) were screened using specific search terms. Relevant literature was identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria. Effect size information (odds ratio and the corresponding 95% confidence interval [CI]) was obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. Statistical analysis was performed with the Stata sofz (Version 13.0) software.Overall, 17 case-control studies involving 7129 CRC patients and 7710 healthy control subjects satisfied the criteria for inclusion in the meta-analysis. There was no significant association between ABCB1 3435C>T polymorphism and CRC risk in any of the genetic models. In the CC versus CT model (I = 20.9%, Pheterogeneity = .276), CC versus CT + TT model (I = 45.6%, Pheterogeneity = .102) and CT versus CC + TT model (I = 17.8%, Pheterogeneity = .298) analyses, between-study heterogeneities were detected as significant in Asian populations. In the CT versus TT model (I = 24%, Pheterogeneity = .254) and CC + CT versus TT model (I = 0, Pheterogeneity = .55), between-study heterogeneities were found to be significant in groups of different populations.The meta-analysis described here suggests that the ABCB1 3435C>T polymorphism is not related to CRC susceptibility.