The association between CD2+ peripheral blood lymphocyte subsets and the relapse of bladder cancer in prophylactically BCG-treated patients

We investigated the potential existence of differences in the distribution of T-lymphocyte subsets and in the proliferative response of these CD2+ cells to polyclonal mitogens in patients with transitional cell bladder carcinoma (SBTCC) treated with prophylactic intracavitary instillations of bacillus Calmette–Guérin (BCG) according to their clinical response to this treatment. Before BCG treatment, different subset distribution (CD8+ and CD3+ CD56+), activation antigen expression (CD3+ HLA– DR+) and proliferative response to mitogenic signals were found in CD2+ cells from SBTCC patients prophylactically treated with BCG who remained free of disease or those who had recurrence of tumour. Otherwise, the prophylactic intracavitary BCG instillations in SBTCC patients are associated with a transitory variation of T-lymphocyte subset distribution (CD4 and CD8) and activation antigens expression (CD25). © 1999 Cancer Research Campaig

Enhancing the immunotherapeutic potential of mycobacteria by transfection with tumour necrosis factor-α

In an attempt to enhance the anti-tumour properties of mycobacteria we have developed recombinant forms of Mycobacterium smegmatis which express and secrete biologically active human tumour necrosis factor-α (TNF-α). This was achieved by transfecting M. smegmatis using shuttle plasmids incorporating the cDNA sequence for the human TNF-α mature peptide. In vitro experiments on a panel of human bladder tumour cell lines (EJ18, MGH-U1, RT4, RT112) indicate that our genetically modified mycobacteria are more effective than wild-type at inducing or up-regulating the expression of intracellular adhesion molecule-1 and the secretion of an array of proinflammatory cytokines [interleukin-1 (IL-1), IL-6, IL-8, granulocyte–macrophage colony-stimulating factor]. We have also demonstrated increased adhesion molecule and cytokine expression in response to mycobacteria transfected with vector containing no gene insert. However, this was not as pronounced as that observed following tumour cell stimulation by the TNF-α-transfected strain. In contrast, in three out of four tumour cell lines all M. smegmatis strains were found to down-regulate the secretion of the anti-inflammatory cytokine transforming growth factor-β1. Our studies have also confirmed that M. smegmatis is a powerful inhibitor of bladder tumour cell growth and revealed that its antiproliferative potency is enhanced by transfecting with human TNF-α and, to a lesser extent, with vector alone. All M. smegmatis strains were effective in the activation of peripheral blood leucocyte cultures. However, no differences were observed in the ability of the TNF-α-transfected, mock-transfected and wild-type mycobacteria to induce tumour cell killing activity. These results suggest that the immunomodulatory effects of M. smegmatis can be enhanced by transfection with vectors which allow the secretion of human TNF-α, thus increasing mycobacterial immunotherapeutic potential

The impact of a tailored nutrition intervention delivered for the duration of hospitalisation on daily energy delivery for patients with critical illness (INTENT): a phase II randomised controlled trial

Background: Nutrition interventions commenced in ICU and continued through to hospital discharge have not been definitively tested in critical care to date. To commence a program of research, we aimed to determine if a tailored nutrition intervention delivered for the duration of hospitalisation delivers more energy than usual care to patients initially admitted to the Intensive Care Unit (ICU). Methods: A multicentre, unblinded, parallel-group, phase II trial was conducted in twenty-two hospitals in Australia and New Zealand. Adult patients, requiring invasive mechanical ventilation (MV) for 72–120 h within ICU, and receiving < 80% estimated energy requirements from enteral nutrition (EN) were included. The intervention (tailored nutrition) commenced in ICU and included EN and supplemental parenteral nutrition (PN), and EN, PN, and/or oral nutrition after liberation from MV, and was continued until hospital discharge or study day 28. The primary outcome was daily energy delivery from nutrition (kcal). Secondary outcomes included duration of hospital stay, ventilator free days at day 28 and total blood stream infection rate. Main results: The modified intention to treat analysis included 237 patients (n = 119 intervention and n = 118 usual care). Baseline characteristics were balanced; the median [interquartile range] intervention period was 19 [14–35] and 19 [13–32] days in the tailored nutrition and usual care groups respectively. Energy delivery was 1796 ± 31 kcal/day (tailored nutrition) versus 1482 ± 32 kcal/day (usual care)—adjusted mean difference 271 kcal/day, 95% CI 189–354 kcal. No differences were observed in any secondary outcomes. Conclusions: A tailored nutrition intervention commenced in the ICU and continued until hospital discharge achieved a significant increase in energy delivery over the duration of hospitalisation for patients initially admitted to the ICU. Trial registration ClinicalTrials.gov Identifier NCT03292237. First registered 25th September 2017. Last updated 10th Feb 2023