Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells

Abstract

A 29-year-old female breast cancer patient with multiple bone metastases (HLA-A2) was treated with adoptive transfer using autologous peripheral blood mononuclear cells (PBMCs) activated with the HLA-A2-matched allogeneic GC022588 gastric cancer cell line and interleukin-2 plus an immobilized anti-CD3 antibody culture system. The relief of bone pain in parallel with a decrease of serum carcinoembryonic antigen levels was obtained just after the administration of GC022588-activated effector lymphocytes, and a good quality of life was accomplished for 4 months. The GC022588-activated effector lymphocytes included 44% CD4 + , 77% CD8 + , and 26% CD4 + CD8 + phenotypes, and expressed 25% killing activity against GC022588 stimulator cells at an E/T ratio of 50:1. T cell receptor (TCR) usage analysis for the effector cells showed oligoclonal expression of TCRVß1, 3, 9, and 11, especially TCRVß5.2, 12, 13.1 and 17, and their killing activity was significantly inhibited in the presence of anti-TCR•ß antibody and anti-TCRVß12 antibody. SSCP analysis revealed clonotypic bands of TCRVß12. These results suggest that shared antigens exist between breast and gastric adenocarcinomas. Allogeneic tumor cells can stimulate PBMCs to generate effector cells with selected TCRCDR3 usages that recognize tumor antigens. These effector lymphocytes may be good candidates for the adoptive immunotherapy of cancer.

Design of Peptide-Based Vaccines for Cancer

“…Furthermore, in mouse models, immunization with H-2K b -binding mEphA2 682-689 , and I-A b -binding mEphA2 [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] loaded DC in C57BL/6 mice induced specific CTL lysis in vitro. Mice immunized with peptides, EphA2 671-679 , EphA2 682-679 , or EphA2 [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] peptides showed protection against a EphA2 negative B16 tumor challenge and induced significant suppression of lung metastases after challenge with B16-BL6 tumor cells [183]. Mechanism of EphA2 protection was due to inhibition of vascular endothelial growth factor (VEGF) induced angiogenesis.…”

“…However, it is becoming increasingly evident that the presence of systemic antibodies that recognize tumor antigens such as MUC1 may offer a survival advantage in patients with cancer [37]. Passively administered naked mouse, human, chimeric or humanized antibodies that fix complement or have ADCC activity have shown some promise and the most impressive results have been generated with the antibodies, Trastuzumab (Herceptin®) and Rituximab (Rituxan®) [38][39][40][41]. An immunoconjugate of CD33 and calicheamycin has also given good responses in patients with acute myelogenic leukemia and is approved by the FDA [42].…”

In vivo distribution and antitumor effect of infused immune cells in a gastric cancer model

“…After priming by antigen presented by antigen presenting cells, CTLs can recognize and kill corresponding target cells (35,36). Adoptive transfer of antitumor CTLs has already been employed in clinical trials and has shown to be effective in adoptive immunotherapy of ovarian cancer, melanoma, breast cancer and renal carcinoma (12,(37)(38)(39)(40). In this study, CTL cells were derived from PBMCs and stimulated by DCs loaded with BGC823 tumor cell lysate.…”