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Bacterial immunotherapy in bronchial asthma.

In the treatment of bronchospastic states, primary bacterial bronchial asthma and asthmatic bronchitis, one of the most controversial aspects is the use of bacterial vaccines. In general, the treatment of these conditions is symptomatic, neglecting for the most part the existing bacterial allergy. At present, as a result of great advances in the immunotherapy of these disorders, the importance of an allergic response to bacteria in the etiology of these bronchopathies is beyond doubt. The subjects were 120 patients, 59 women and 51 men, with ages ranging from 7 to 73 years. Of this group, 21 were children less than 12 years old and all had a diagnosis of bronchial asthma or asthmatic bronchitis, with or without paranasal sinusitis, and exclusively of bacterial etiology. In order to study and evaluate the effectiveness of immunotherapy, a questionnaire, reproduced in fig. 1 was sent to the patients three years after the beginning of treatment. For this study, only the answers to this questionnaire were considered. Examination of the results shows that in bronchial disorders with bacterial allergy, treatment with bacterial vaccine achieves a 75% success rate. In the small group of children studied (a larger group is currently under investigation), the results are even more satisfactory, reaching 90.47%. It is noteworthy that the immediate reaction to the skin test was positive (++ to ++++) in 83.32% of the cases. Of the greatest importance also is the associated paranasal sinusitis in 83% of the cases, part of a sinobronchopulmonary syndrome which contributes substantially to this state of bacterial allergy. Significant side effects were found in 52.6% of the patients and consisted mainly of slight catarrhal symptoms, apparent at the beginning of treatment. At present, we have no doubt whatsoever that immunotherapy is much more valuable than prolonged symptomatic therapy in the treatment of primary bacterial bronchial asthma.

Adolescent↗
PubMed2026

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans↗
PubMed2026

Deletion of the Salmonella pathogenicity island 2 gene, spiC, in attenuated Salmonella Typhimurium VNP20009 optimizes its potential for bacterial schwannoma therapy.

UNLABELLED: Recent advances in systems biology and immunotherapy have spurred the investigation of bacteria as therapeutic vehicles for cancer treatment. Currently, Bacillus Calmette-Guérin remains the only FDA-approved bacterial cancer therapy; it is a live attenuated mycobacterium that is indicated for the treatment and prophylaxis of carcinoma in situ of the urinary bladder and for the prophylaxis of primary or recurrent papillary tumors following transurethral resection. Although safety concerns have been raised, attenuated Salmonella Typhimurium strains such as VNP20009 have advanced to clinical trials targeting fast-growing human tumors. Notably, this strain induces robust immunological control of slow-growing tumors such as NF2-related schwannomatosis (NF2-SWN) in preclinical murine models. Here, we genetically characterize VNP20009 with the goal of constructing genetically defined attenuated strains that retain its promising therapeutic features while improving safety. Specifically, we investigated the contribution of the Salmonella pathogenicity island I (SPI-1) and SPI-2 type III secretion systems to antitumor efficacy and biosafety. Mutation of the SPI-1 gene sipB, a key structural component required for SPI-1 type III secretion system function, partially reduced tumor control in NF2-SWN murine schwannoma models, suggesting that bacterial invasion alone does not fully account for antitumor activity. In contrast, deletion of the SPI-2 gene spiC, a key effector required for intracellular survival, preserved robust tumor regression in NF2-SWN murine schwannoma models while improving safety and reducing systemic toxicity. To create a genetically defined and tractable platform, we generated two attenuated strains-AST101 and AST101-ΔspiC-which retain key mutations present in VNP20009 but lack ill-characterized background mutations. In the syngeneic NF2-SWN mouse schwannoma model, both strains significantly suppressed tumor growth compared to PBS. Collectively, these findings support the development of rationally engineered Salmonella Typhimurium strains with enhanced safety and preserved antitumor efficacy. IMPORTANCE: Given long-standing safety concerns surrounding the therapeutic use of live bacteria, we constructed a ΔspiC mutant of VNP20009 and demonstrated that it provides a markedly improved safety profile while retaining antitumor efficacy in NF2-related schwannomatosis mouse schwannoma models. In addition, we created two genetically defined Salmonella Typhimurium strains, AST01 and AST01-ΔspiC, which incorporate the key-targeted mutations found in VNP20009 and VNP20009-ΔspiC, respectively. These engineered strains offer a well-defined genetic background, enabling precise investigation of the bacterial traits responsible for Salmonella Typhimurium-mediated tumor control and thus further improvement of attenuated strains optimized for bacteriotherapy of neoplasms.

Salmonella typhimurium↗
PubMed2026

Bacterial Outer Membrane Vesicles in Colorectal Cancer: Interdomain Communication Hubs in Pathogenesis and Immunotherapy.

The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs)-nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms-have emerged as critical long-range signaling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift toward exploiting next-generation probiotic and engineered OMVs as highly tunable therapeutic platforms. By combining cutting-edge bioengineering strategies-such as biomimetic mineralization to neutralize local tissue acidity and chemotherapeutic packaging-these nanovectors effectively reprogram the immunosuppressive tumor microenvironment (TME). Specifically, optimized OMVs modulate macrophage polarization from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically "cold" tumors "hot." Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.

Colon cancer↗
PubMed1979

Active, specific immunotherapy of murine leukemia. II. Adjuvant effect of Corynebacterium parvum.

We have previously shown that irradiated LSTRA cells (LX) were immunogenic and could prolong survival of mice bearing LSTRA tumors. This study demonstrated that addition of Corynebacterium parvum to the LX dramatically improved the strength of tumor immunity. In pretreatment-challenge experiments, C. parvum augmented the immunogenicity of 10(6) LX given intradermally, with an optimum dose of 0.14-1.4 microgram C. parvum per mouse. In therapy experiments (intraperitoneal vaccine treatment after tumor cell challenge), the therapeutic effect of 10(7) LX was improved by admixture of C. parvum, leading to a larger number of cured mice, permitting treatment of a larger challenge inoculum, and allowing later initiation of treatment than was possible with LX alone. Optimal dose of C. parvum for therapy was 1,400 microgram per mouse. Presensitization to C. parvum or use of repeated vaccine injections did not further improve the therapeutic effect. Cure of tumor-bearing mice by the mixed vaccine was tumor-specific. These results suggest that C. parvum is a potent adjuvant for use in active, tumor-specific immunotherapy.

Adjuvants, Immunologic↗
PubMed1979

Tumoricidal effects of Mycobacterium ulcerans toxin on murine adenocarcinoma (C3HBA).

Fresh homogenized mammary gland adenocarcinoma (C3HBA) material was subcutaneously inoculated in the anterior right thigh of transplant host mice (C3H/HeJ). When tumors were palpable, the mice were separated into three groups. The test group received biweekly intratumoral injections of Mycobacterium ulcerans filtrate containing 40 mg of protein per ml. One control group received intratumoral injections of normal physiological saline, and the remaining group received no treatment at all. The survival rate of toxin-treated animals was 13.5% at 15 weeks when compared with the control groups. Additionally, tumor metastasis was apparently abrogated in test animals when compared to the control animals. Marked necrosis of the tumors in the test animals was noted by histological examination. Controls showed slight to moderate degrees of tumor necrosis. In this model Mycobacterium ulcerans toxin appears to have therapeutic value as an antitumor agent.

Adenocarcinoma↗