Phase II trial of Belagenpumatucel-L, a TGF-β2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients
Abstract
In a previous dose escalation trial we demonstrated dose related survival correlation to Belagenpumatucel-L. In order to further evaluate safety and response at the previously defined optimal dose and schedule and to gain preliminary evidence on a hypothesis that the level of circulating tumor cells (CTCs) in blood may correlate with the overall survival of patients with stage IV NSCLC, we initiated a phase II trial. Patients received intradermal immunization of 2.5 x 10(7) transfected allogeneic tumor cells (Belagenpumatucel-L, supplied by NovaRx) 1 x every month for a total of 16 months. Circulating tumor cells (Veridex, Raritan, NJ) were measured every 4 weeks. Twenty-one advanced NSCLC patients were enrolled on this study. No significant toxic effect was observed. Overall survival was 562 days. The median survival was 660 days in patients having less than 2 CTCs at baseline compared to 150 days in patients with 2 or more CTCs (P=0.025). Phase II results of safety and response are consistent with prior experience following treatment with Belagenpumatucel-L and there is a suggestion that the number of circulating tumor cells at baseline appears to correlate with overall survival. A larger clinical trial is warranted to further explore this observation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A phase 3 clinical trial of the anti-sense TGF-β2 vaccine did not meet its endpoint of increased overall survival.
“a phase 3 clinical trial did not meet its endpoint of increased overall survival371.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [371]
Cites
Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer
Cristofanilli, M., Budd, G. T., Ellis, M. J., Stopeck, A., Matera, J., Miller, M. C., Reuben, J. M., Doyle, G. V., Allard, W. J., Terstappen, L. W. M. M., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040766 · Cited by 4,602 · see citing works
Allard, W. J., Matera, J., Miller, M. C., Repollet, M., Connelly, M. C., Rao, C., Tibbe, A. G. J., Uhr, J. W., & Terstappen, L. W. M. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0378 · Cited by 2,542 · see citing works
Cohen, S. J., Punt, C. J. A., Iannotti, N. O., Saidman, B. H., Sabbath, K. D., Gabrail, N. Y., Picus, J., Morse, M., Mitchell, E. P., Miller, M. C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.8923 · Cited by 1,843 · see citing works
Transforming Growth Factor-β: Biological Function and Chemical Structure
Sporn, M. B., Roberts, A. B., Wakefield, L. M., & Assoian, R. K. (1986) · Science · doi:10.1126/science.3487831 · Cited by 1,173 · see citing works
Transforming growth factor-beta in disease: the dark side of tissue repair.
Border, W. A., & Ruoslahti, E. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115821 · Cited by 1,096 · see citing works
Braun, S., Pantel, K., Müller, P. E., Janni, W., Hepp, F., Kentenich, C. R. M., Gastroph, S., Wischnik, A., Dimpfl, T., Kindermann, G., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002243420801 · Cited by 923 · see citing works
Deactivation of macrophages by transforming growth factor-β
Tsunawaki, S., Sporn, M. B., Ding, A. H., & Nathan, C. (1988) · Nature · doi:10.1038/334260a0 · Cited by 862 · see citing works
Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer
Budd, G. T., Cristofanilli, M., Ellis, M. J., Stopeck, A., Borden, E. C., Miller, M. C., Matera, J., Repollet, M., Doyle, G. V., Terstappen, L. W. M. M., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1769 · Cited by 776 · see citing works
The TGF-β family of growth and differentiation factors
Massagué, J. (1987) · Cell · doi:10.1016/0092-8674(87)90443-0 · Cited by 672 · see citing works
Circulating Tumor Cell Number and Prognosis in Progressive Castration-Resistant Prostate Cancer
Danila, D. C., Heller, G., Gignac, G. A., Gonzalez-Espinoza, R., Anand, A., Tanaka, E., Lilja, H. G., Schwartz, L. B., Larson, S. M., Fleisher, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1506 · Cited by 665 · see citing works
Rook, A. H., Kehrl, J. H., Wakefield, L. M., Roberts, A. B., Sporn, M. B., Burlington, D. B., Lane, H. C., & Fauci, A. S. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.10.3916 · Cited by 570 · see citing works
Heiser, A., Coleman, D., Dannull, J., Yancey, D., Maurice, M. A., Lallas, C. D., Dahm, P., Niedzwiecki, D., Gilboa, E., & Vieweg, J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214364 · Cited by 562 · see citing works
Heiser, A., Coleman, D., Dannull, J., Yancey, D. R., Maurice, M. A., Lallas, C. D., Dahm, P., Niedzwiecki, D., Gilboa, E., & Vieweg, J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14364 · Cited by 487 · see citing works
Bodmer, S., Strommer, K., Frei, K., Siepl, C., de Tribolet, N., Heid, I., & Fontana, A. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.143.10.3222 · Cited by 386 · see citing works
Constam, D. B., Philipp, J., Malipiero, U., ten Dijke, P., Schachner, M., & Fontana, A. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.5.1404 · Cited by 373 · see citing works
Nemunaitis, J. J., Dillman, R. O., Schwarzenberger, P. O., Senzer, N. N., Cunningham, C. C., Cutler, J., Tong, A., Kumar, P., Pappen, B. O., Hamilton, C., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.5335 · Cited by 365 · see citing works
Self-citationFakhrai, H., Dorigo, O., Shawler, D. L., Lin, H., Mercola, D., Black, K. L., Royston, I., & Sobol, R. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.2909 · Cited by 334 · see citing works
Self-citationCytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant.
Fehm, T. N., Sagalowsky, A. I., Clifford, E., Beitsch, P. D., Saboorian, H. M., Euhus, D., Meng, S., Morrison, L. E., Tucker, T. F., Lane, N., et al. (2002) · PubMed · Cited by 308 · see citing works
Soiffer, R. J., Hodi, F. S., Haluska, F. G., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.07.005 · Cited by 306 · see citing works
Salgia, R., Lynch, T. J., Skarin, A. T., Lucca, J. V., Lynch, C., Jung, K., Hodi, F. S., Jaklitsch, M. T., Mentzer, S. J., Swanson, S., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.03.091 · Cited by 296 · see citing works
Nemunaitis, J. J., Sterman, D. H., Jablons, D. M., Smith, J. W., Fox, B. A., Maples, P. B., Hamilton, S., Borellini, F., Lin, A., Moralı, S., et al. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh028 · Cited by 243 · see citing works
Self-citationAngiogenesis as an unfavorable prognostic factor in human colorectal carcinoma
Takebayashi, Y., Akiyama, S., Yamada, K., Akiba, S., & Aikou, T. (1996) · Cancer · doi:10.1002/(sici)1097-0142(19960715)78:2 · Cited by 222 · see citing works
Kong, F., Jirtle, R. L., Huang, D. H., Clough, R. W., & Anscher, M. S. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19991101)86:9 · Cited by 133 · see citing works
Kasid, A., Bell, G. I., & Director, E. P. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.2.690 · Cited by 116 · see citing works
Vaccines in cancer: GVAX®, a GM-CSF gene vaccine
Nemunaitis, J. J. (2005) · Expert Review of Vaccines · doi:10.1586/14760584.4.3.259 · Cited by 114 · see citing works
Self-citationSoria, J., Gauthier, L., Raymond, É., Granotier, C., Morat, L., Armand, J., Boussin, F. D., & Sabatier, L. (1999) · PubMed · Cited by 89 · see citing works
Hirte, H. W., & Clark, D. A. (1991) · Cancer Immunology Immunotherapy · doi:10.1007/bf01789047 · Cited by 72 · see citing works
Lissoni, P., Meregalli, S., Fossati, V., et al. (1994) · Tumori Journal · doi:10.1177/030089169408000611 · Cited by 63 · see citing works
Ruffini, P. A., Rivoltini, L., Silvani, A., Boiardi, A., & Parmiani, G. (1993) · Cancer Immunology Immunotherapy · doi:10.1007/bf01742258 · Cited by 61 · see citing works
Jakowlew, S. B., Mathias, A., Chung, P., & Moody, T. W. (1995) · PubMed · Cited by 54 · see citing works
NAGANUMA, H., SASAKI, A., SATOH, E., NAGASAKA, M., NAKANO, S., ISOE, S., TASAKA, K., & NUKUI, H. (1996) · Neurologia medico-chirurgica · doi:10.2176/nmc.36.789 · Cited by 42 · see citing works
The development of immunotherapies for non-small cell lung cancer
Salgaller, M. L. (2002) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2.3.265 · Cited by 32 · see citing works
Stojadinovic, A., Mittendorf, E. A., Holmes, J. P., et al. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-007-9538-x · Cited by 28 · see citing works
Ratto, G. B., Cafferata, M. A., Scolaro, T., et al. (2000) · Journal of Immunotherapy · doi:10.1097/00002371-200001000-00019 · Cited by 17 · see citing works
Katoh, M., Neumaier, M., Nezam, R., et al. (2004) · PubMed · Cited by 16 · see citing works
Technology evaluation: BLP-25, Biomira Inc.
Morse, M. A. (2001) · PubMed · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Targeting the TGFβ signalling pathway in disease
Akhurst, R. J., & Hata, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3810 · Cited by 1,466 · see citing works
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Targeting TGFβ signal transduction for cancer therapy
Liu, S., Ren, J., & ten Dijke, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00436-9 · Cited by 413 · see citing works
“Lucanix (belagenpumatucel-L) is a vaccine expressing AON TGFβ2 RNA that was evaluated in clinical trial studies for NSCLC patients.(246,247) This vaccine did not meet its survival endpoint in a phase 3 clinical trial for NSCLC patients; however, it improved the overall survival of patients who had completed chemothera…”
MethodTransforming growth factor‐β in stem cells and tissue homeostasis
Xu, X., Zheng, L., Yuan, Q., Zhen, G., Crane, J. L., Zhou, X., & Cao, X. (2018) · Bone Research · doi:10.1038/s41413-017-0005-4 · Cited by 414 · see citing works
Giaccone, G., Bazhenova, L. A., Nemunaitis, J., Tan, M., Juhász, E., Ramlau, R., van den Heuvel, M. M., Lal, R., Kloecker, G. H., Eaton, K. D., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.07.035 · Cited by 279 · see citing works
Self-citationTransforming growth factor-β: a therapeutic target for cancer
Haque, S., & Morris, J. C. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1327107 · Cited by 276 · see citing works
Therapeutic cancer vaccines: Are we there yet?
Klebanoff, C. A., Acquavella, N., Yu, Z., & Restifo, N. P. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00979.x · Cited by 271 · see citing works
Kras and tumor immunity: friend or foe?
Cullis, J., Das, S., & Bar-Sagi, D. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031849 · Cited by 85 · see citing works
Genetic Modification of the Lung Directed Toward Treatment of Human Disease
Sondhi, D., Stiles, K. M., De, B. P., & Crystal, R. G. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.152 · Cited by 36 · see citing works
- Authors
- Nemunaitis, J., Nemunaitis, M., Senzer, N., Snitz, P., Bedell, C., Kumar, P., Pappen, B., Maples, P. B., Shawler, D., & Fakhrai, H.
- Affiliations
- Mary Crowley Cancer Research Center (US)
- Baylor University Medical Center (US)
- Gradalis (United States) (US)
- NovaRx (United States) (US)
- Corresponding author
- Nemunaitis, J
- ORCID
- Nemunaitis, J
- Venue
- Cancer Gene Therapy
- Published
- 2009-03-13
- Volume
- 16
- Issue
- 8
- Pages
- 620-624
- ISSN
- 0929-1903 (ISSN-L)
- 1476-5500
- OpenAlex
- W1993615391
- Cited by
- 147
- References
- 36
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 11 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 8 · 2015: 11 · 2014: 17 · 2013: 19 · 2012: 15
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- non-small cell lung cancer, circulating tumor cells, overall survival, intradermal vaccination, gene-modified tumor cells, vaccine safety, stage IV NSCLC
- MeSH terms
- Adult, Aged, Carcinoma, Non-Small-Cell Lung, Dose-Response Relationship, Drug, Female, Humans, Injections, Intradermal, Lung Neoplasms, Male, Middle Aged, Tumor Cells, Cultured, Genetic Therapy, DNA, Antisense, Disease Progression, Cancer Vaccines, Transforming Growth Factor beta2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review