Activated T-cell and bispecific antibody immunotherapy for high-risk breast cancer. Bench to bedside.
Nontoxic approaches are needed to improve overall survival (OS) and progression-free survival (PFS) for high-risk breast cancer. Combination immunotherapy (IT) consisting of activated T cells (ATC), interleukin-2 (IL-2), and CTL (GM-CSF) was given after peripheral blood stem cell transplant (PBSCT). There were no major toxicities and there appear to be improvements in OS and PFS over historical controls. In order to develop specific cytotoxic T lymphocytes (CTL), we combined ATC with the use of bispecific antibody (BiAb). By arming ATC with anti-CD3 x anti-HER2/neu BiAb (HER2BiAb), the approach converts nonspecific ATC into HER2/neu (HER2) specific CTL. ATC remain armed, kill tumor targets for days, and produce cytokines after binding to tumor. Arming ATC with BiAbs may prove to be effective for targeting a variety of tumors with and without high-dose chemotherapy.
Lum
L G
LG
Roger Williams Cancer Center, Providence, RI 02908, USA. lawrenceglum@cs.com
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D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000628:therapy*; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000637:transplantation*; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007376:Interleukin-2; D018719:Erb-b2 Receptor Tyrosine Kinases