Daniel Vallera, PhD
University of Minnesota Masonic Cancer Center, Department of Radiation Oncology
425 E. River Road
Room 460B
Minneapolis, MN 55455
United States
The goal of our laboratory is to advance the field of cancer by genetically engineering and testing new biological drugs against chemotherapy refractory cancer. These new drugs kill by a mechanism entirely different than chemotherapy. We believe that we are in a unique position to address some of the most pressing issues including the engagement of the innate immune system to kill cancer. A new genre of drugs show that cancer metastasis can effectively be combated by engaging the immune system to selectively kill tumors. We developed a new drug platform that works extremely well in recruiting NK cells to kill leukemia cells. In addition to my conventional laboratory, I am fortunate to have a cGMP laboratory that manufactures FDA compliant drugs for phase 1 testing. We published our first clinical trial with one of these drugs in Clinical Cancer Research. We have an accomplished team of experts that can help this integrated effort succeed. Our laboratory has an established track-record in animal models and I have a background in immunology, experimental therapeutics, molecular biology, radiation oncology, and gene therapy that has served us well. Over the last 35 years, I have built my career and reputation on cell selective drug targeting and am recognized as a major contributor to the field. My immunology and molecular biology background has served me well and my team has published over a hundred and eighty PubMed papers. Our success in translational research is evidenced by our bringing targeted drugs to phase 1 clinical trial. The most recent targeted toxin will now enter phase 2 testing. We currently have active INDs and are treating patients at the University of Minnesota Cancer Center. I have a demonstrated a record of successful and productive research projects in an area of translational, biological drug development and serve as inventor on several patents held by the University of Minnesota.
Expertise
Biologic Drug Development, Genetic Engineering, Immunotherapy, Radiation Biology Research, Bispecific Antibodies, Targeted Therapy
FDA Consultant
Awards & Recognition
Designated Lion Scholar-Lion Research Award
Randy Shaver Cancer Research Fund – 2016 Angel Award
Past Leukemia Society of America Scholar
Pierce Targeted Therapy Award
NIH REACH Award- 2016
Professional Associations
American Association of Immunologists
Transplantation Society
American Society of Hematology
Education
Professor of Therapeutic Radiology-Radiation Oncology, Department of Radiation Oncology
Lions Scholar of Molecular Therapeutics
Associate Professor of Therapeutic Radiology
Assistant Professor of Therapeutic Radiology, Department of Radiation Oncology
Faculty, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program
Faculty, PhD Program in Medical Physics
Faculty, MS and PhD Programs in Pharmacology
Research Associate, University of Minnesota
Postdoctoral Fellow, University of Minnesota
PhD, Ohio State University (Microbiology), 1978
MS, Ohio State University (Microbiology), 1975
BS, Ohio State University (Microbiology), 1973
Research
Research Summary/Interests
Transplantation, cancer, leukemia, molecular therapeutics, gene therapy
Our laboratory specializes in the design and development of new anti-cancer biologic agents with the goal of getting them into the clinic as quickly as possible. Typically, new hybrid proteins are synthesized by combining genes encoding cancer cell binding domains with genes encoding molecules that deliver death signals. The resulting proteins selectively bind to cancer cells, internalize the death signal, and kill the cancer cells. Thus, they provide cancer specific therapy in a manner that chemotherapeutic agents cannot. These new anti-cancer agents are primarily directed to overexpressed signal markers on the surface of cancer cells and we have successfully produced promising fusion proteins that can kill brain tumors, breast cancer, leukemia, and cells causing organ rejection. In order to facilitate the delivery of these agents at the site of the tumor, another approach under study uses gene therapy. We are fashioning retroviruses containing our target genes and using them to infect tumor reactive T cells. The T cells have the ability to migrate to tumor and secrete the anti-cancer molecule at site where they can have the greatest effect. Another facet of our work focuses on the use of targeting powerful beta irradiation-emitting radionuclides, to cancer cells. Certain isotopes can be conjugated to cancer cell binding antibodies in such a way that they can selectively bind to tumors and cause their regression. In this instance, internalization of these molecules into cells are unnecessary. The cross-fire effect is potent enough to destroy even large tumors and the side effects seem tolerable. Through the design and production of these new molecules we hope to not only devise urgently needed alternative cancer therapies, but to further our understanding of the intricacies of protein engineering.
Research Funding Grants
NIH REACH (Research Evaluation and Commercialization Hub) Award (U01)
Minnesota Ovarian Cancer Alliance
NIH/NCI R01- (30 years)
Immunotoxins in bone marrow transplantation 1/1/1984—4/30/2016
Lion Drug Development Foundation
William Lawrence-Blanches Hughes Foundation
University of Minnesota, Office of Technology, Committee on Pharmaceutical Development Award
Randy Shaver Foundation
Special Radiation Oncology Project Development Award
Publications
- 1.Vallera DA, Felices M, McElmurry R, McCullar V, Zhou X, Schmohl J, Zhang B, Lenvik A, Panoskaltsis-Mortari A, Verneris MR, Tolar J, Cooley S, Weisdorf DJ, Blazar BR, Miller JS. IL-15 Trispecific Killer Engagers (TriKEs) Make NK Cells Specific to CD33+ Targets While Also Inducing Persistence, In Vivo Expansion, and Enhanced Function. Clin Cancer Res. 2016. In Press.
- This paper selected as 2016 Editors Choice by the Journal Science Translational Medicine. Roxana Dronca, Turning BiKEs into TriKEs to fight cancer. Science Translational Medicine 2016 8:328
- 2.Schmohl JU, Vallera DA. CD133, Selectively Targeting the Root of Cancer. Toxins (Basel). 2016 May 28;8(6). pii: E165.
- 3.Felices M, Lenvik TR, Davis ZB, Miller JS, Vallera DA. Generation of BiKEs and TriKEs to improve NK Cell-Mediated Targeting of Tumor Cells. Methods Mol Biol. 2016;1441:333-46.
- 4.Schmohl JU, Felices M, Taras E, Miller JS, Vallera DA. Enhanced ADCC and NK Cell Activation of an Anticarcinoma Bispecific Antibody by Genetic Insertion of a Modified IL-15 Cross-linker. Mol Ther. 2016 Aug;24(7):1312-22.
- 5.Bachanova V, Frankel AE, Cao Q, Lewis D, Grzywacz B, Verneris MR, Ustun C, Lazaryan A, McClune B, Warlick E, Kantarjian H, Weisdord DD, Miller JS, Vallera DA. Phase 1 study of a bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies. Clin Cancer Res. 2015;21:1267-72.
- 6.Schmohl JU, Gleason MK, Dougherty PR, Miller JS, Vallera DA. Heterodimeric Bispecific Single Chain Variable Fragments (scFv) Killer Engagers (BiKEs) Enhance NK-cell Activity Against CD133+ Colorectal Cancer Cells. Target Oncol. 2015. In Press. PMID: 26566946
- 7.Schmohl JU, Todhunter D, Oh S, Vallera DA. Mutagenic Deimmunization of Diphtheria Toxin for Use in Biologic Drug Development. Toxins (Basel). 2015 Oct 10;7:4067-82. PMID: 26473923
- 8.Huang J, Li YM, Cheng Q, Vallera DA, Hall WA.A novel brain metastasis xenograft model for convection?enhanced delivery of targeted toxins via a micro?osmotic pump system enabled for real?time bioluminescence imaging. Mol Med Rep. 2015 Oct;12:5163-8 PMID: 26238362
- 9.Shen J, Vallera DA, Wagner CR. Prosthetic Antigen Receptors. J Am Chem Soc. 2015 Aug 19;137:10108-11. PMID: 26230248
- 10.Waldron NN, Barsky SH, Dougherty PR, Vallera DA. A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma. Target Oncol. 2014 Sep;9:239-49. PMID: 23900680
- 11.Gleason MK, Ross JA, Warlick ED, Lund TC, Verneris MR, Wiernik A, Spellman S, Haagenson MD, Lenvik AJ, Litzow MR, Epling-Burnette PK, Blazar BR, Weiner LM, Weisdorf DJ, Vallera DA, Miller JS. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood. 2014 May 8;123(19):3016-26. PMID: 24652987
- 12.Gleason MK, Ross JA, Warlick ED, Lund TC, Verneris MR, Wiernik A, Spellman S, Haagenson MD, Lenvik AJ, Litzow MR, Epling-Burnette PK, Blazar BR, Weiner LM, Weisdorf DJ, Vallera DA, Miller JS. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells from MDS patients against primary MDS and MDSC CD33+ targets. Blood. 2014 Mar 20. [Epub ahead of print] PMID: 24652987. PMCID: PMC4014844
- 13. Vallera DA, Jin N, Yanqun S, Panoskaltsis-Mortari A, Kelekar A, and Chen W. Retroviral immunotoxin gene therapy of leukemia in mice using leukemia-specific T cells transduced with an IL-3/Bax fusion protein gene Human Gene Therapy 14:1787-1798, 2003
- 14. Li C, Hall WA, Jin N, Todhunter DA, Panoskaltsis-Mortari A, Vallera DA. Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein in vitro and in vivo in nude mice. Protein Eng. 2002 May;15(5):419-427.
- 15. Vallera DA, Li C, Jin N, Panoskaltsis-Mortari A, Hall WA. Targeting urokinase-type plasminogen activator receptor on human glioblastoma tumors with diphtheria toxin fusion protein DTAT. J Natl Cancer Inst. 2002 Apr 17;94(8):597-606.
- 16. Jin N, Chen W, Blazar BR, Ramakrishnan S, Vallera DA. Gene therapy of murine solid tumors with T cells transduced with a retroviral vascular endothelial growth factor--immunotoxin target gene. Hum Gene Ther. 2002 Mar 1;13(4):497-508. pdf
- 17. Vallera DA. Gene therapy with immunotoxins. Methods Mol Biol. 2001;166:235-46. Review