Innate immune therapy with a Bacillus Calmette-Guérin cell wall skeleton after radical surgery for non-small cell lung cancer: a case-control study.
ABSTRACT We investigated whether adjuvant immunotherapy with Bacillus Calmette-Guérin (BCG) cell wall skeleton (CWS) and surgical resection was better than resection, with or without other adjuvant therapy, for patients with non-small cell lung cancer (NSCLC).
The case group comprised 71 patients who underwent radical surgery for NSCLC, followed by BCG-CWS immunotherapy, with follow-up data available. The case-control study was designed with one control selected for each case-group patient. Each control was matched by pathological stage and year of birth (+/-5 years). BCG-CWS 200 microg was inoculated intracutaneously in the upper arm four times per week (sensitization phase); then at 4-week intervals (therapeutic phase).
The case-group patients received 45 +/- 22.6 (average +/- SD) cycles of BCG-CWS inoculation. Overall 5-year and 10-year survival rates were 71% and 61% for the case-group patients, and 63% and 43% for the control-group patients. The survival rate of the case group was better than that of the control group (not significant; P = 0.114). The same trend was seen in the patients with stage III or N+ NSCLC (not significant; P = 0.114, P = 0.168). There were no life-threatening adverse events.
BCG-CWS immunotherapy seemed to improve survival after resection of NSCLC, especially locally advanced NSCLC. Moreover, this immunotherapy did not compromise quality of life during treatment.
SourceAvailable from: Takatomo SatohAdvancements in Tumor Immunotherapy and Cancer Vaccines, 02/2012; , ISBN: 978-953-307-998-1
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ABSTRACT: As well as its local effects, radiotherapy leads to the delayed regression of distant non-irradiated lesions. These abscopal effects are most likely mediated by the innate immune system. Patient 1, a 74-year-old male, had concomitant left supraclavicular lymph node metastases and multiple lung metastases 2 years after complete resection of pathological stage IIA (T1bN1M0) lung adenocarcinoma. He received radiation therapy (RT) of 58 Gy for the supraclavicular lymph node metastases and then innate immunotherapy using the cell wall skeleton of Mycobacterium bovis bacillus Calmette–Guérin (BCG-CWS). Three months after the RT and 2 months after the immunotherapy, all lung metastases disappeared on computed tomography scans. Patient 2, a 40-year-old female, underwent stereotactic body RT (SBRT) for metastasis from a deep-seated urothelial carcinoma in the right upper lobe of the lung. Twenty-one months after the SBRT, we started administration of BCG-CWS to two new lesions that had appeared in the left lung. As a result, after 3 months, the lesions completely disappeared. Complete response was maintained for more than 1 year in both patients. We believe that an optimal combination of RT and immunotherapy will elicit abscopal effects that can be employed to attain a systematically achievable, rather than anecdotal, therapeutic goal.04/2013; DOI:10.1007/s13691-013-0130-x
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ABSTRACT: Materials used for the past 30 years as immunoadjuvants induce suboptimal antitumor immune responses and often cause undesirable local inflammation. Some bacterial lipopeptides that act as Toll-like receptor (TLR) 2 ligands activate immune cells as immunoadjuvants and induce antitumor effects. Here, we developed a new dendritic cell (DC)-targeting lipopeptide, h11c (P2C-ATPEDNGRSFS), which uses the CD11c-binding sequence of intracellular adhesion molecule-1 to selectively and efficiently activate DCs but not other immune cells. Although the h11c lipopeptide activated DCs similarly to an artificial lipopeptide, P2C-SKKKK (P2CSK4), via TLR2 in vitro, h11c induced more effective tumor inhibition than P2CSK4 at low doses in vivo with tumor antigens. Even without tumor antigens, h11c lipopeptide significantly inhibited tumor growth and induced tumor-specific cytotoxic T cells. P2CSK4 was retained subcutaneously at the vaccination site and induced severe local inflammation in in vivo experiments. In contrast, h11c was not retained at the vaccination site and was transported into the tumor within 24 h. The recruitment of DCs into the tumor was induced by h11c more effectively, while P2CSK4 induced the accumulation of neutrophils leading to severe inflammation at the vaccination site. Because CD11b+ cells, but not CD11c+ cells, produced neutrophil chemotactic factors such as macrophage inflammatory protein (MIP)-2 in response to stimulation with TLR2 ligands, the DC-targeting lipopeptide h11c induced less MIP-2 production by splenocytes than P2CSK4. In this study, we succeeded in developing a novel immunoadjuvant, h11c, which effectively induces antitumor activity without adverse effects such as local inflammation via the selective activation of DCs. © 2014 Wiley Periodicals, Inc.International Journal of Cancer 12/2014; 135(12). DOI:10.1002/ijc.28939 · 5.01 Impact Factor