Treatment Of Superficial Bladder Cancer Research Articles

Mucoadhesive Thiolated Hyaluronic Acid/Pluronic F127 Nanogel Formation via Thiol-Maleimide Click Reaction for Intravesical Drug Delivery.

The development of nanocarriers to prolong the residence time and enhance the permeability of chemotherapeutic drugs on bladder mucosa is important in the postsurgery treatment of superficial bladder cancers (BCs). Here, the mucoadhesive HA-SH/PF127 nanogels composed of a temperature-sensitive Pluronic F127 (PF127) core and thiolated hyaluronic acid (HA-SH) shell were prepared by the emulsification/solvent evaporation method. The nanogels were constructed through the thiol-maleimide click reaction in the HA-SH aqueous side of the oil-water interface and self-oxidized cross-linking thiols between HA-SH. The HA-SH/PF127 nanogels prepared at different thiol-to-maleimide group molar ratios, water-to-oil volume ratios, and cross-linking reaction times were characterized regarding hydrodynamic diameter (Dh) and zeta potential (ζ), and the optimal formulation was obtained. The excellent mucoadhesive properties of the HA-SH/PF127 nanogels were evaluated by using the mucin particle method. Doxorubicin (DOX) was encapsulated in the PF127 core of DOX@HA-SH/PF127 nanogels with a high loading efficiency (87.5%) and sustained release from the nanogels in artificial urine. Ex vivo studies on porcine bladder mucosa showed that the DOX@HA-SH/PF127 nanogels enhanced the penetration of the DOX into the bladder mucosa without disrupting the mucus structure or the bladder tissue. A significant dose-dependent cytotoxic effect of DOX@HA-SH/PF127 nanogels on both T24 and MB49 cells was observed. The present study demonstrates that the mucoadhesive HA-SH/PF127 nanogels are a promising intravesical drug delivery system for superficial BC therapy.

Miliary Pulmonary Tuberculosis After Intravesical BCG Instillation in a Patient with High-Grade Bladder Cancer

Intravesical administration of Bacillus Calmette-Guerin (BCG) vaccine is used in the treatment of superficial bladder cancer. In clinical practice, intravesical BCG immunotherapy after transurethral tumor resection is a highly effective treatment option in preventing tumor recurrence and progression in medium and high risk superficial bladder tumors. Since patients are given live tuberculosis (TB) bacillus, serious side effects such as pneumonia, sepsis and even death can be seen. Lung involvement occurs in less than 1% of patients and most commonly presents as interstitial pneumonia or miliary TB. Miliary TB is difficult to diagnose and is usually based on high clinical suspicion, as Mycobacterium bovis is not isolated in most cases. Treatment is not completely standardized. However, in severe cases, a combination of antituberculosis drugs and corticosteroids is recommended. In this report, a case of miliary tuberculosis, a very rare complication after instillation of BCG into the bladder in a patient with a diagnosis of superficial bladder cancer, was presented. A 73-year-old male patient diagnosed with bladder tumor underwent transurethral resection of bladder tumor, and then weekly intravesical injection of BCG-MEDAC for six weeks had no adverse effects. Three weeks of intravesical BCG supplementation was planned for the patient who had no signs of recurrence when checked three months later by cystoscopy. Two hours after the first dose, the patient, who applied to the emergency department with the complaint of chills and shivering, was hospitalized for further follow-up and treatment. Afterwards, repeat cultures were taken from the patient whose fever continued on the seventh day of treatment with broad-spectrum antibiotics (meropenem and teicoplanin). In addition, when abdominal and thorax computed tomography (CT) were performed, multiple miliary nodular lesions were detected in both lungs and were evaluated in favor of miliary TB. With these findings, the patient was started on miliary TB therapy [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STM)] targeting Mycobacterium bovis, since it was an infection that developed after BCG injection. In the third week of the treatment, the patient's fever was under control, and he was discharged on the 25th day of his hospitalization because of significant improvement in infection markers [C-reactive protein(CRP)-procalcitonin]. At the end of two months, there was clear regression of pulmonary abnormalities on control thorax CT. In conclusion, miliary TB developing after intravesical BCG instillation is a very rare condition, the cause of which is not fully understood, the etiology of fever can be easily missed, and the diagnosis is difficult. In addition, this case is presented to draw attention to a critical disease that requires long treatment and follow-up and requires attention.

Role of Intravesical BCG as a Therapeutic Vaccine for Treatment of Bladder Carcinoma

Bacterial products have attracted much attention as potential antitumor agents, with the ability to provide direct tumoricidal effects, leading to the inhibition of tumor growth. Treatment of superficial bladder cancer with intravesical BCG has a more reduction potential than surgery in tumor recurrence rate. BCG, the gold standard for NMIBC, is manufactured from different strains and produced commercially with varied strengths. There are a few countries known as the manufacturer of this strategic biopharmaceutical product, and Iran as a member of the Eastern Mediterranean Region plays a vital role in supplying this vaccine. Studies have failed to uncover the exact mechanism of action of the intravesical BCG; however, evidence points toward an immunogenic mechanism that proficiently modifies a biologic response and provokes the immune cells in order to kill and suppress tumors. Among various underlying mechanisms, BCG bacillus attachment to fibronectin through its FAP is a pivotal mechanism for BCG tumoricidal activity

Targeting Bladder Urothelial Carcinoma with pHLIP-ICG and Inhibition of Urothelial Cancer Cell Proliferation by pHLIP-amanitin.

Acidity is a useful biomarker for the targeting of metabolically active-cells in tumors. pH Low Insertion Peptides (pHLIPs) sense the pH at the surfaces of tumor cells and can facilitate intracellular delivery of cell-permeable and cell-impermeable cargo molecules. In this study we have shown the targeting of malignant lesions in human bladders by fluorescent pHLIP agents, intracellular delivery of amanitin toxin by pHLIP for the inhibition of urothelial cancer cell proliferation, and enhanced potency of pHLIP-amanitin for cancer cells with 17p loss, a mutation frequently present in urothelial cancers. Twenty-eight ex-vivo bladder specimens, from patients undergoing robotic assisted laparoscopic radical cystectomy for bladder cancer, were treated via intravesical incubation for 15-60 minutes with pHLIP conjugated to indocyanine green (ICG) or IR-800 near infrared fluorescent (NIRF) dyes at concentrations of 4-8 μM. White light cystoscopy identified 47/58 (81%) and NIRF pHLIP cystoscopy identified 57/58 (98.3%) of malignant lesions of different subtypes and stages selected for histopathological processing. pHLIP NIRF imaging improved diagnosis by 17.3% (p < 0.05). All carcinoma-in-situ cases missed by white light cystoscopy were targeted by pHLIP agents and were diagnosed by NIRF imaging. We also investigated the interactions of pHLIP-amanitin with urothelial cancer cells of different grades. pHLIP-amanitin produced concentration- and pH-dependent inhibition of the proliferation of urothelial cancer cells treated for 2 hrs at concentrations up to 4 μM. A 3-4x enhanced cytotoxicity of pHLIP-amanitin was observed for cells with a 17p loss after 2 hrs of treatment at pH6. Potentially, pHLIP technology may improve the management of urothelial cancers, including imaging of malignant lesions using pHLIP-ICG for diagnosis and surgery, and the use of pHLIP-amanitin for treatment of superficial bladder cancers via intravesical instillation.

Intravesical Therapy of Superficial Urothelial Bladder Cancer with BCG and Epirubicin 50 Mg - Comparative Analysis

Summary Bladder cancer is a heterogeneous disease in molecular, histological and clinical aspects. Treatment should also be considered from different angles - surgery, intravesical chemo- or immunotherapy, radiation therapy and lifestyle changes. Intravesical treatment of superficial bladder cancer with Еpirubicin or Bacillus Calmette-Guérin (BCG) is a continuation of surgical treatment to reduce or eliminate further recurrence.

MILIARY PNEUMONITIS AND INTRAVESICULAR BACILLUS CALMETTE-GUERIN TREATMENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Bacillus Calmette-Guérin (BCG) is a live attenuated strain of the aerobic bacterium Mycobacterium bovis. Although the mechanism of action by which intravesical BCG elicits anti-tumorigenicity remains elusive, it is a mainstay adjunct treatment of superficial bladder cancer. Non-infectious symptoms including dysuria, hematuria, and fevers are experienced in ~85% of individuals treated. Disseminated mycoplasma infections are reported in less than 5% of patients administered this intravesicular regimen. Most of these infections involve genitourinary structures, but rarely BCG-associated pneumonitis can occur. CASE PRESENTATION: A 59 year-old gentleman presented to urology with gross hematuria. Cystoscopy and biopsy revealed carcinoma in situ with a poorly differentiated transitional cell carcinoma. Transurethral resection of the tumor was performed followed by induction and maintenance therapy with monthly treatments of intravesicular BCG. The patient initially tolerated the BCG treatments quite well, but after two treatment cycles developed an unexplained cough and dyspnea with associated night sweats. A seven-day course of levofloxacin was prescribed for empiric treatment of presumed community acquired pneumonia (CAP). Unfortunately, the patient's symptomatology was recalcitrant to CAP therapy. A high-resolution CT of the chest was performed which demonstrated miliary tuberculosis. Tuberculin skin testing prior to the initiation of BCG was found to be negative. As a guidance counselor, he worked alongside students and fellow faculty at a local high school. He had no recent international travel, prior incarceration, or any other risk factors associated with TB. The decision was made to administer isoniazid and rifampin for treatment of miliary pneumonitis found to be Mycobacterium bovis in origin. The patient's symptomatology resolved following a six-month course the aforementioned regimen. Follow up imaging demonstrated improvement of the previously visualized ground glass opacities in addition to three subcentimeter pulmonary nodules remained. Surveillance imaging after an additional six months showed resolution of the ground glass opacities and pulmonary nodule stability. DISCUSSION: Pulmonary Mycobacterium dissemination is a rare yet grave complication of intravesicular BCG used for the treatment of superficial bladder cancer. The recognition and differentiation of BCG-associated pneumonitis from CAP and Mycobacterium tuberculosis is essential for appropriate pharmacologic intervention, especially since Mycobacterium bovis is resistant to some traditional Mycobacterium drugs. CONCLUSIONS: This case explores the critical features involved in the diagnosis and treatment of BCG-associated miliary pneumonitis. REFERENCE #1: Lamm DL. Complications of bacillus Calmette-Guérin immunotherapy. Urol Clin North Am. 1992 Aug;19(3):565-72. PMID: 1636240. REFERENCE #2: Ghandi NM, Morales A, Lamm DL. Bacillus Clamette-Gurin immunotherapy for genitourinary cancer. BJU int. 2013 Aug;112(3):288-97. doi: 10.1111/j.1464-410X.2012.11754.x. Epub 2013 Mar 20. PMID: 23517232 REFERENCE #3: Sylvester RJ, van der Meijden AP, Witjes JA, Kurth K. BCG versus chemotherapy for the intravescal treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials. J Urol. 2005 Jul;174(1):86-91; discussion 91-2. doi: 10.1097/01.ju.0000162059.64886.1c. PMID: 15947584 DISCLOSURES: No relevant relationships by Paul Dugdale, source=Web Response No relevant relationships by Daniel Santone, source=Web Response

A solitary pulmonary nodule caused by Mycobacterium tuberculosis var. BCG after intravesical BCG treatment: a case report

BackgroundIntravesical instillation of bacillus Calmette–Guérin (BCG) as a treatment for superficial bladder cancer rarely causes pulmonary complications. While published cases have been pathologically characterized by multiple granulomatous lesions due to disseminated infection, no case presenting as a solitary pulmonary nodule has been reported.Case presentationA man in his 70 s was treated with intravesical BCG for early-stage bladder cancer. After 1 year, he complained of productive cough with a solitary pulmonary nodule at the left lower lobe of his lung being detected upon chest radiography. His sputum culture result came back positive, with conventional polymerase chain reaction (PCR) identifying Mycobacterium tuberculosis complex. However, tuberculosis antigen-specific interferon-gamma release assay came back negative. Considering a history of intravesical BCG treatment, multiplex PCR was conducted, revealing the strain to be Mycobacterium tuberculosis var. BCG. The patient was then treated with isoniazid, ethambutol, levofloxacin, and para-aminosalicylic acid following an antibiotic susceptibility test showing pyrazinamide resistance, after which the size of nodule gradually decreased.ConclusionThis case highlights the rare albeit potential radiographic presentation of Mycobacterium tuberculosis var. BCG, showing a solitary pulmonary nodule but not multiple granulomatous lesions, after intravesical BCG treatment. Differentiating Mycobacterium tuberculosis var. BCG from Mycobacterium tuberculosis var. tuberculosis is crucial to determine whether intravesical BCG treatment could be continued for patients with bladder cancer.

Re: Association between Treatment of Superficial Bladder Cancer and 10-Year Mortality in Older Adults with Multiple Chronic Conditions.

Re: Association between Treatment of Superficial Bladder Cancer and 10-Year Mortality in Older Adults with Multiple Chronic Conditions.

Diagnostic and Prognostic Potential of Biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in Bladder Cancers.

The high occurrence of bladder cancer and its tendency to recur in combination with a lifelong surveillance make the treatment of superficial bladder cancer one of the most expensive and time-consuming. Moreover, carcinoma in situ often leads to muscle invasion with an unfavorable prognosis. Currently, invasive methods including cystoscopy and cytology remain a gold standard. The aim of this study was to explore urine-based biomarkers to find the one with the best specificity and sensitivity, which would allow optimizing the treatment plan. In this review, we sum up the current knowledge about Cytokeratin fragments (CYFRA 21.1), Excision Repair Cross-Complementation 1 (ERCC1), Tumour Protein p53 (Tp53), Fibroblast Growth Factor Receptor 3 (FGFR3), Tumor-Associated Trypsin Inhibitor (TATI) and their potential applications in clinical practice.

Mucoadhesive nanoparticles based on ROS activated gambogic acid prodrug for safe and efficient intravesical instillation chemotherapy of bladder cancer

Chemotherapy is the standard of care for bladder cancer after transurethral resection of the tumor. However, the rapid excretion of clinically used formulations of anticancer drugs make the common intravesical instillation chemotherapy far from efficient. Therefore, improving the muco-adhesion and penetrability of chemotherapeutic drugs became the key factors in the post-surgery treatment of superficial bladder cancers. Here, a reduction sensitive vehicle was developed to deliver the reactive oxygen species activated prodrug of gambogic acid for treatment of orthotopic bladder cancer. The positively charged chitosan can significantly enhance the adhesion and permeability of prodrug within the bladder wall. Moreover, by utilizing the different glutathione and ROS level between cancer cells and normal cells, the dual responsive nanoparticle can selectively and rapidly deliver drug in bladder cancer cells, and thus can significantly inhibit the proliferation of bladder cancer cells in an orthotopic superficial bladder cancer model without causing damage to normal cells. This work demonstrates that the smart prodrug nanomedicine may act as a promising drug-delivery system for local chemotherapy of bladder cancer with unprecedented clinical benefits.

Elevated release of inflammatory but not sensory mediators from the urothelium is maintained following epirubicin treatment

Intravesical treatment of superficial bladder cancer with epirubicin is associated with local urological adverse effects, the causes of which are unknown. Our aim was to investigate the effects of epirubicin on the release of urothelial mediators and inflammatory cytokines. UROtsa cells were treated with epirubicin for 1 h at 37 °C. Release of urothelial transmitters and inflammatory cytokines was examined immediately, 24 h and 7 days following treatment. Release of ATP and nitric oxide were increased transiently after treatment with epirubicin (0.01 mg/ml), but this was not evident one-week after treatment. Basal prostaglandin E2 release was decreased at 24 h but not at 7 days. An increase in basal acetylcholine release and decrease in stretch-induced acetylcholine release were observed 24-h after treatment (0.01 mg/ml). One week following epirubicin treatment (0.001 mg/ml), stretch-induced, but not basal acetylcholine release, was observed. Secretion of interleukin-6 and interleukin-8 was increased 70-fold and 5-fold respectively, at 24 h (0.01 mg/ml). This was sustained and one week after epirubicin treatment (0.001 mg/ml), the increase in the secretion of both inflammatory cytokines was still evident.Epirubicin treatment induces several transient changes in urothelial function. However, the increased secretion of inflammatory cytokines (IL-6 and IL-8) is sustained and these mediators may be involved in the pathophysiology of bladder toxicity following intravesical epirubicin treatment.

The impact of using intraoperative photodynamic diagnosis on the prognosis of bladder cancer

Photodynamic Diagnosis (PDD) is widely used today for the diagnosis and treatment of superficial bladder cancer. This study aimed to analyse the impact of using this technique on recurrence rate, residual tumour rate and progression-free survival. We conducted this study retrospectively in our unit between 10/2014 and 02/2018. We divided our patients into 2 groups: white light group, 49 patients who underwent primary bladder tumour resection with white light transurethral resection of bladder tumour (WL-TURB), and blue light group, 49 patients treated with blue light transurethral resection of bladder tumour (BL-TURB) with PDD. Patients in both groups were followed up for one year. We collected data for tumour recurrence for the first year, 3-month and 1-year relapse-free survival and 1-year progression-free assessment pursuant to the EORTC risk classification by Sylvester 2006. Furthermore, the residual tumour rate was determined by re-TURB. The following results were found independent of age, gender and histological findings: Residual tumour rate: blue light group 13.95 % vs. white light group 32.6 %, (p 0.02, OR 3.8, CI 95 % [1.17 - 12.85]).; 3-month relapse-free survival: blue light group 87.7 % vs. white light group 67.4 % (p 0.02, HR 3.18, CI 95 % [1.20 - 8.42]); 1-year relapse-free survival: blue light group 77.6 % vs. white light group 55.1 % (p 0.015, HR 2.56, CI 95 % [1.20 - 5.45]); 1-year progression-free survival: blue light group 95.9 % vs. white light group 79.6 %, p 0.03, HR 5.23, CI 95 % [1.11 - 24.53]) CONCLUSION: The use of hexaminolevulinate significantly reduces the risk of residual tumours compared with conventional TURB. The PDD technique significantly improved 3- and 12-month recurrence-free survival, especially in low and medium-risk tumours, and 1-year progression-free survival, especially in high-risk tumours.

Bacillus Calmette-Guérin (BCG)-Cell Wall Skeleton as Immunotherapeutic Option for BCG-Refractory Superficial Bladder Cancer

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water- soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system. Key Words: Bacillus Calmette-Guérin; Cell wall skeleton; Bladder cancer; Adjuvant immunotherapy; Drug delivery system.

Additional Extension of the Mathematical Model for BCG Immunotherapy of Bladder Cancer and Its Validation by Auxiliary Tool

Abstract Immunotherapy with bacillus Calmette–Guérin (BCG) is a classic treatment for superficial bladder cancer. Although BCG instillation is a well-established protocol, some patients do not respond to this treatment. To model improvement of this protocol, Bunimovich-Mendrazitsky (B-M) et al. provided a platform for in silico testing of modified protocols of BCG instillation and combination with IL-2. The purpose of this work is to improve and further develop this BCG model describing the tumor–immune interactions occurring in the bladder in response to BCG and IL-2 therapies, based on novel clinical data. To validate this BCG model, we used the results of BCG treatment of 10 patients with bladder cancer 3-5 years ago. Individual data for each patient was entered to simulate the model. As a result, a treatment protocol was obtained which coincided with the protocol assigned by the doctor. In addition, cancer cell growth graphs were obtained from the model simulations, which coincided with the clinical conclusions of the patient’s treatment outcome. Moreover, the program provides a more optimal treatment protocol for each patient. We show that calculated protocols from the model can prevent excess side effects of immunotherapy and even of unnecessary death for some patients, informing the clinical potential of our model.

Miliary tuberculosis induced by intravesical instillation of bacillus Calmette-Guérin

The intravesical instillation of bacillus Calmette-Guérin (BCG) is an efficacious complementary treatment for superficial bladder cancer after transurethral resection. This treatment delays progression, decreases the probability that the patient will have to undergo cystectomy in the future, and improves survival; it is generally efficacious and well tolerated.Among the most common local complications are irritative symptoms, hematuria, local genitourinary infection. Systemic complications are much less common.We present the case of a 71-year-old man who developed miliary tuberculosis secondary to treatment with intravesical bacillus Calmette-Guérin for bladder cancer. This is exceptionally uncommon complication is potentially lethal and requires the immediate discontinuation of treatment.

Short Review on Treatment of Superficial Bladder Cancer (Ta, Tis, T1)

Short Review on Treatment of Superficial Bladder Cancer (Ta, Tis, T1)

BCG-induced discitis and osteomyelitis in a patient with a history of bladder cancer

This article describes the diagnosis and treatment of a patient with lumbar discitis and osteomyelitis caused by Bacillus Calmette-Guérin instillation therapy for treatment of superficial bladder cancer. Treatment of this rare condition consists of antituberculosis microbial therapy and one or more IV antibiotics to cover multidrug-resistant bacteria in the bone.

Tuberculosis miliar inducida por instilación endovesical de bacilo de Calmette-Guérin

The intravesical instillation of bacillus Calmette-Guérin (BCG) is an efficacious complementary treatment for superficial bladder cancer after transurethral resection. This treatment delays progression, decreases the probability that the patient will have to undergo cystectomy in the future, and improves survival; it is generally efficacious and well tolerated.Among the most common local complications are irritative symptoms, hematuria, local genitourinary infection. Systemic complications are much less common.We present the case of a 71-year-old man who developed miliary tuberculosis secondary to treatment with intravesical bacillus Calmette-Guérin for bladder cancer. This is exceptionally uncommon complication is potentially lethal and requires the immediate discontinuation of treatment.

Prognostic analysis of TURBT combined with epirubicin in the treatment of superficial bladder cancer

Objective To investigate the effect of transurethral resection of bladder tumor (TURBT) combined with epirubicin for the serum vascular endothelial growth factor (VEGF) level and survival prognosis in patients with superficial bladder cancer. Methods From June 2011 to June 2016, 100 patients with superficial bladder cancer were selected in our hospital. All patients were randomly divided into mitomycin group and epirubicin group, 50 cases in each group, mitomycin group was treated with 40 mg mitomycin after the operation, epirubicin group was treated with 50 mg epirubicin after the operation. Results VEGF levels of mitomycin group and epirubicin group at 3, 6 months after treatment were significantly lower than those of the before treatment, VEGF levels of epirubicin group were significantly lower than those of mitomycin group at 3, 6 months after treatment, the difference was statistically significant (P 0.05). Cumulative survival rate of epirubicin group was significantly higher than those of mitomycin group, and cumulative recurrence rate of epirubicin group was significantly lower than those of mitomycin group at 1 year, 2 years, 3 years, and the difference was statistically significant (P<0.05). Conclusions TURBT combined epirubicin can effectively reduce postoperative recurrence and improve survival prognosis in patients with bladder cancer, it may be associated with reducing the serum VEGF level in patients, and it has a good safety, it's worth for further clinical promotion. Key words: Urinary Bladder Neoplasms; Cystectomy; Epirubicin; Prognosis

Immunotherapeutic Potential of Mollusk Hemocyanins in Combination with Human Vaccine Adjuvants in Murine Models of Oral Cancer.

Mollusk hemocyanins have been used for decades in immunological and clinical applications as natural, nontoxic, nonpathogenic, and nonspecific immunostimulants for the treatment of superficial bladder cancer, as carriers/adjuvants of tumor-associated antigens in cancer vaccine development and as adjuvants to dendritic cell-based immunotherapy, because these glycoproteins induce a bias towards Th1 immunity. Here, we analyzed the preclinical therapeutic potential of the traditional keyhole limpet hemocyanin (KLH) and two new hemocyanins from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH) in mouse models of oral squamous cell carcinoma. Due to the aggressiveness and deadly malignant potential of this cancer, the hemocyanins were applied in combination with adjuvants, such as alum, AddaVax, and QS-21, which have been shown to be safe and effective in human vaccines, to potentiate their antitumor activity. The immunogenic performance of the hemocyanins in combination with the adjuvants was compared, and the best formulation was evaluated for its antitumor effects in two murine models of oral cancer: MOC7 cells implanted in the flank (heterotopic) and bioluminescent AT-84 E7 Luc cells implanted in the floor of the mouth (orthotopic). The results demonstrated that the hemocyanins in combination with QS-21 showed the greatest immunogenicity, as reflected by a robust, specific humoral response predominantly characterized by IgG2a antibodies and a sustained cellular response manifesting as a delayed hypersensitivity reaction. The KLH- and FLH-QS-21 formulations showed reduced tumor development and greater overall survival. Hemocyanins, as opposed to QS-21, had no cytotoxic effect on either oral cancer cell line cultured in vitro, supporting the idea that the antitumor effects of hemocyanins are associated with their modulation of the immune response. Therefore, hemocyanin utilization would allow a lower QS-21 dosage to achieve therapeutic results. Overall, our study opens a new door to further investigation of the use of hemocyanins plus adjuvants for the development of immunotherapies against oral carcinoma.