Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
Study Design
2.2. Immune Response Measurement
2.2.1. Anti-eVim Antibody ELISA
2.2.2. Immunofluorescence
2.3. Patient Monitoring and Evaluation
2.4. Statistical Analysis
3. Results
3.1. Expression of Vimentin in Urothelial Carcinoma
3.2. Study Population
3.3. Anti-eVim Antibody Response
3.4. Clinical Response Data
3.5. Adverse Events
3.6. Reactivity of CVx1 Sera with Mouse and Human Vimentin
4. Discussion
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Dogs (n) | Gender, n (%) | Breed, n (%) | Weight, Median | Age, Average | Prior Tx * | Stage, n (%) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
M | F | Single | Mixed | kg (range) | year (range) | n (%) | T2N0M0 | T2N1M0 | T2N0M1 | T2N2M1 | T3N0M0 | T3N1M1 | ||
Study | 20 | 8 (40%) | 12 (60%) | 17 (85%) | 3 (15%) | 18.8 (4.4–72) | 11 (7–14) | 5 (25%) | 15 (75%) | 2 (10%) | 2 (10%) | 1 (5%) | 0 (0%) | 0 (0%) |
Ctrl | 31 | 12 (39%) | 19 (61%) | 25 (81%) | 6 (19%) | 14.4 (3.6–47) | 11 (6–15) | 6 (19%) | 24 (75%) | 2 (6%) | 2 (6%) | 0 (0%) | 1 (3%) | 2 (6%) |
Dogs | N1, N2/M1 | CR | PR | SD | PD | PFI | OS | Refs. | |
---|---|---|---|---|---|---|---|---|---|
Total/Evaluable or Tumor Response | Any Metastasis, % of Total | ||||||||
Drugs | (#) | (%) | (%) | (%) | (%) | (%) | days | days | |
Current study | |||||||||
CVx1/meloxicam | 25/20 | 5/5/10 | 10 | 10 | 75 | 5 | 257 | 374 | |
Randomized trials | |||||||||
Vinblastine/piroxicam | 27/26 | 0/4/4 | 0 | 58 | 33 | 8 | 199 | 299 | [26] |
Cisplatin/piroxicam | 14/14 | 28/14/43 | 14 | 57 | 28 | 0 | 124 | 246 | [27] |
Mitoxantrone/piroxicam | 26/NA | 8/NA/8 | 0 | 8 | 69 | 23 | 106 | 247 | [28] |
Carboplatin/piroxicam | 24/NA | 29/NA/29 | 0 | 13 | 54 | 33 | 73 | 263 | [28] |
Single-arm trials | |||||||||
Piroxicam | 34/34 | 9/15/24 | 2 | 4 | 18 | 10 | NA | 181 | [29] |
Mitoxantrone/piroxicam | 55/48 | NA/NA/11 | 2 | 33 | 46 | 19 | 194 | 291 | [30] |
Carboplatin/piroxicam | 31/29 | 13/13/19 | 0 | 38 | 45 | 17 | NA | 161 | [21] |
Doxorubicin/piroxicam | 34/23 | NA/NA/NA | 0 | 9 | 60 | 30 | 103 | 168 | [31] |
Gemcitabine/piroxicam | 38/37 | 11/3/11 | 5 | 22 | 51 | 22 | NA | 230 | [32] |
Dogs *, n = 20 (%) | Vaccinations, n = 172 (%) | ||||||
---|---|---|---|---|---|---|---|
Initial, n =79 | Maintenance, n = 66 | ||||||
Grade 1 | Grade 2 | Grade 3–5 | Grade 1 | Grade 2 | Grade 1 | Grade 2 | |
Administration site conditions | |||||||
Injection site reactions | 9 (45%) | 7 (35%) | 0 (0%) | 27 (34%) | 8 (10%) | 10 (15%) | 5 (8%) |
Lameness local extremity | 5 (25%) | 1 (5%) | 0 (0%) | 2 (3%) | 0 (0%) | 0 (0%) | 0 (0%) |
Constitutional clinical signs | |||||||
Lethargy | 3 (15%) | 5 (25%) | 0 (0%) | 7 (9%) | 6 (6%) | 0 (0%) | 1 (2%) |
Anorexia | 1 (5%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (2%) | 0 (0%) |
Nausea/vomiting | 5 (25%) | 0 (0%) | 0 (0%) | 4 (5%) | 0 (0%) | 3 (5%) | 0 (0%) |
Fever | 2 (10%) | 0 (0%) | 0 (0%) | 4 (5%) | 0 (0%) | 0 (0%) | 0 (0%) |
Diarrhea | 2 (10%) | 0 (0%) | 0 (0%) | 1 (1%) | 0 (0%) | 1 (2%) | 0 (0%) |
Any * | 11 (55%) | 8 (40%) | 0 (0%) | 12 (60%) | 5 (25%) | 5 (25%) | 4 (20%) |
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Engbersen, D.J.M.; van Beijnum, J.R.; Roos, A.; van Beelen, M.; de Haan, J.D.; Grinwis, G.C.M.; Schalken, J.A.; Witjes, J.A.; Griffioen, A.W.; Huijbers, E.J.M. Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs. Cancers 2023, 15, 3958. https://doi.org/10.3390/cancers15153958
Engbersen DJM, van Beijnum JR, Roos A, van Beelen M, de Haan JD, Grinwis GCM, Schalken JA, Witjes JA, Griffioen AW, Huijbers EJM. Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs. Cancers. 2023; 15(15):3958. https://doi.org/10.3390/cancers15153958
Chicago/Turabian StyleEngbersen, Diederik J. M., Judy R. van Beijnum, Arno Roos, Marit van Beelen, Jan David de Haan, Guy C. M. Grinwis, Jack A. Schalken, J. Alfred Witjes, Arjan W. Griffioen, and Elisabeth J. M. Huijbers. 2023. "Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs" Cancers 15, no. 15: 3958. https://doi.org/10.3390/cancers15153958