Bladder cancer treatment with vaccines
Articles in Press, Accepted Manuscript, Available Online from 09 June 2026
https://doi.org/10.61882/jct.2026.2064491.2097
Fatemeh Rezaei, Maedeh Tamimi, mohammad javad dehghan esmatabadi, Ali Asghar Deldar
Abstract Bladder cancer is one of the most common malignancies of the urinary tract and originates from the bladder epithelium. Despite advances in surgery, chemotherapy, radiation, and immunotherapy, bladder cancer remains a major clinical challenge because of its high recurrence rate, risk of progression, and the need for long-term surveillance and repeated interventions. In recent years, vaccine-based immunotherapy has gained increasing attention as a promising strategy for improving antitumor immune responses, reducing relapse, and enhancing therapeutic outcomes across different disease stages.
Bacillus Calmette–Guérin (BCG) is the first and most established vaccine used in bladder cancer treatment and remains the standard intravesical adjuvant immunotherapy for non muscle invasive bladder cancer (NMIBC). Its antitumor activity is largely mediated by immunomodulatory effects within the bladder microenvironment, including activation of innate immune cells, induction of pro inflammatory cytokines, and subsequent priming of adaptive immune responses that support cytotoxic T cell–mediated tumor control. However, a substantial proportion of patients experience intolerance, inadequate response, recurrence, or resistance, underscoring the need for next generation vaccine strategies with improved specificity and durability.
Accordingly, several emerging vaccine platforms have been investigated. Cell based vaccines, particularly dendritic cell (DC) vaccines, aim to exploit the antigen presenting function of DCs to enhance tumor specific T cell activation using tumor lysates, defined tumor associated antigens, or engineered immunostimulatory constructs. In parallel, monoclonal antibody–based approaches that target tumor associated antigens have been explored as immunotherapeutic tools that may complement vaccine-induced immunity. Peptide vaccines provide a more defined strategy by stimulating antigen specific responses against selected epitopes, and their performance may be strengthened through the use of appropriate adjuvants, optimized epitope selection, and improved delivery systems. More recently, mRNA vaccines have attracted considerable interest because they enable rapid and flexible design, can encode one or multiple tumor antigens, and may induce robust cellular immunity. These platforms also offer opportunities for personalization based on patient specific antigenic profiles and may be manufactured in a scalable manner.
Combination therapy is an important direction in this field. Pairing vaccine approaches with immune checkpoint inhibitors (e.g., PD 1/PD L1 blockade) may enhance therapeutic efficacy by reversing tumor mediated immune suppression and improving the magnitude and durability of antitumor responses. In addition, integrating vaccines with conventional modalities such as chemotherapy or radiotherapy may further augment immunogenicity through increased antigen release, activation of danger signaling pathways, and immune priming, thereby potentially converting immunologically “cold” tumors into more responsive disease states.
This review summarizes major vaccine strategies investigated for bladder cancer, including BCG, cell based vaccines, peptide vaccines, and mRNA vaccines, and discusses their proposed mechanisms, advantages, and current limitations. Despite encouraging progress, key challenges remain, including tumor heterogeneity, antigen loss, immune evasion, optimization of delivery and dosing schedules, manufacturing complexity, and cost. Future research should focus on refining antigen discovery and vaccine design, identifying predictive biomarkers for patient selection and response monitoring, optimizing combination regimens to maximize synergy, and conducting larger, well designed clinical studies to support clinical translation. Overall, vaccine-based immunotherapy represents a rapidly evolving and promising avenue that may contribute to more effective, durable, and individualized treatment of bladder cancer for patients across disease stages.
Cloning and surface display of xylose dehydrogenase from Caulobacter vibrioides Via E.coli transmembrane protein YiaT
Volume 17, Issue 1, Spring 2026, Pages 1-16
https://doi.org/10.66224/JCT.17.1.1
haniyeh Karamipoor, mohammad javad dehghan esmatabadi, aliasghar Deldar, fatemeh bozorgmehr
Abstract Introduction: Concern over fossil energy costs and environmental deterioration, along with energy security, has created a strong motivation for research and development of routes to provide sustainable, renewable fuels. In recent years, the use of biomass to produce highly valued chemicals has attracted widespread attention. lignocellulosic biomass, as a promising renewable resource for biofuel production, has distinct advantages in terms of economic and environmental aspects. The conversion of renewable raw materials to hydrocarbon fuels is an attractive alternative to fossil fuels from an economic and environmental point of view. The production process of lignocellulosic biomass mainly consists of biomass accumulation, biomass decomposition, simple sugars, and conversion of sugars to biofuel. One of the crucial steps in the economic success of lignocellulosic biofuels depends on the inhibition of competitive metabolism in microorganisms to achieve high productivity. To date, a growing focus is on the use of S. cerevisiae and E. coli as cell lines. These two cellular factories have the benefits that are well known.
Aim: The organic compound D-1,2,4-Butanetriol is a valuable chemical with wide-ranging applications in various fields. The chemical synthesis routes for BT have many drawbacks. By genetically modifying microorganisms, the metabolic pathway for producing many substances, including BT, can be engineered. The organic compound D-1,2,4-butanediol (BT) is an important intermediate chemical widely used in fields such as pharmaceuticals, paper, polymer materials, and military applications. When D-xylose sugar is provided to the bacterium, it is first converted to an intermediate compound called xylonolactone. This compound itself slowly converts into xylonate through a non-enzymatic reaction. To produce xylonate, the engineered bacteria have received xylose and initially, by a dehydrogenase reaction by the xylose dehydrogenase enzyme, that converts it into an intermediate substance: xylonolactone. The xylonolactone is converted slowly and in a nonenzymatic reaction to xylonate. Xylonate is a five-carbon organic acid. Over the past few years, xylonate has been increasingly being considered as an important chemical due to its potential as an important chemical component. Xylonate has many applications that can be used in the food, chemical, and pharmaceutical industries. Specifically, xylonate can act as a precursor for the synthesis of D-1,2,4-Butanetriol and a decrease in concrete water. E.coli due to fast growth in cheap culture medium, having two enzymes for the bto synthesis and product production in lower 24 hours of fermentation was chosen as the target strain of genetic engineering and metabolism. This study aimed to clone and express xylose dehydrogenase from Caulobacter vibrioides in E.coli. Materials and Methods: At first, to access the bacterial gene sequence, the genome of the target bacterium was extracted. Then, to create a strain expressing the enzymes xylose dehydrogenase and xylonolactonase, the genes for these proteins were amplified from Caulobacter vibrioides CB1 and transferred to E. coli. For this purpose, the target genes were amplified using specifically designed primers via the Polymerase Chain Reaction (PCR) method and initially cloned into a pTZ57cloning vector and then subcloned into pET 26b expression vector. At the final step, the expression of the enzyme was assessed by SDS-PAGE, and the other confirmation was the reduction of NAD+ to NADH, which was used as an activity indicator of the enzyme, as investigated by a change in NADH absorbance at 340 nm. Results: Confirmatory tests were performed to ensure the presence of the gene in the vectors (using restriction enzymes and colony PCR for gene amplification). The expression and activity of the enzyme were analysed. The recombinant protein's presence was confirmed by SDS-PAGE for the xylose dehydrogenase gene, with a molecular weight of 52.2 kDa. The estimated recombinant protein expression levels were approximately 25%. Conclusion: The objective of this research was solely to establish the metabolic pathway for xylonate production in E. coli by surface expression of enzymes in this pathway (xylose dehydrogenase). The results obtained in this study confirm that half of the pathway is active at the cell surface, but further experiments are required to determine the precise production levels and complete the pathway. This study aimed to create a metabolic pathway for producing xylonate in E.coli.
