Devin Lowe Laboratory
About Us
Our work centers on the fascinating areas of tumor immunology and tumor angiogenesis.
There is no question the power of the immune system in preventing or resolving cancer. Decades of pre-clinical work has now matured into viable anti-cancer therapeutics that are showing significant survival benefits in patients. One has to look only as far as gene-engineered effector T cells or specific antibody-based therapies to appreciate the power of the immune system in halting tumorigenesis.
However, we are also readily aware of the immunosuppressive/-evasive nature of the solid tumor microenvironment (TME) that severely diminishes the effectiveness of antibodies and T cells. Established vascularized cancers tend to contain mature and immature vessels that confound blood flow rates within the lesion and promote localized areas of hypoxia and acidosis. The tumor-influenced endothelium also downregulates activating adhesion molecules that ultimately abrogate a T cell’s functional ability to traffick to and localize within the tumor bed. Yet, in cases where the effector T cell gains access to tumor cells, a layered fortress of immunosuppression awaits. TME-residing cells such as regulatory T cells and myeloid-derived suppressor cells elaborate soluble molecules that strip away a T cell’s ability to fight. Immune checkpoints have also received a great deal of attention and involve the TME engaging certain T cell molecules to downmodulate any forthcoming immune response.
So, quite frankly, as the field moves forward to design and implement highly potent cancer immunotherapies, durable clinical responses will be unattainable unless decisive action is also taken against many of the TME-derived properties mentioned above.
To this end, there are two interrelated areas in the lab that receive our focus:
At the basic science level, we are performing studies to understand the mechanistic
aspects and consequences of destroying components of tumor-derived blood vessels using
the immune system. Additionally, we are attempting to improve our knowledge of the
interplay between TME components such as immune cells, cancer cells, and the vasculature.
At the translational science level, we are developing immunotherapeutic strategies
that target tumor angiogenesis with the goal of downstream testing in prospective
clinical trials. We are also creating diagnostic assays to help inform our immunotherapeutic
designs and implementation in patients with cancer.
Research Interest
Basic science level:
- Improve knowledge of the interplay between immune cells, vascular components, and cancer cells
- Understand mechanistic aspects and consequences of tumor blood vessel destruction from immune cells
Translational science level:
- Develop anti-tumor blood vessel immunotherapeutic strategies for individuals with vascularized cancers
The Team
Trevor Anderson Graduate Student/ Research Assistant |
Amanda Wooster Graduate Student/ Research Assistant |
Francis Okpalanwaka Graduate Student / Research Assistant |
Savanna Piersall HSC Lab Worker |
- Storkus WJ, Bose A, Taylor JL, Zhao X, Lowe DB. Immunogenic tumor associated stromal cell antigen peptides and methods of their use. United States Patent # 9,345,770.
- Anderson T, Wooster A, La-Beck I, Saha D, Lowe D. Antibody-drug conjugates: an evolving approach for melanoma treatment. Melanoma research. 2021;31(1):1-17.
- Wooster A, Girgis LH, Brazeale H, Anderson T, Wood L, Lowe D. Dendritic cell vaccine therapy for colorectal cancer. Pharmacological research. 2021;164:105374.
- Wooster AL, Anderson TS, Lowe DB. Expression and characterization of soluble epitope-defined major histocompatibility complex (MHC) from stable eukaryotic cell lines. Journal of immunological methods. 2019;464:22-30.
- Lowe DB, Bivens CK, Mobley AS, Herrera CE, McCormick AL, Wichner T, Sabnani MK, Wood L, Weidanz JA. TCR-like antibody drug conjugates mediate killing of tumor cells with low peptide/HLA targets. mAbs. 2017;9(4):603-614.
- La-Beck I, Jean G, Huynh C, Alzghari SK, Lowe DB. Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy. Pharmacotherapy. 2015;35(10):963-76.
- Lowe DB, Bose A, Taylor JL, Tawbi H, Lin Y, Kirkwood JM, Storkus WJ. Dasatinib promotes the expansion of a therapeutically superior T-cell repertoire in response to dendritic cell vaccination against melanoma. Oncolmmunology. 2014;3(1):e27589.
- Bose A, Lowe DB, Rao A, Storkus WJ. Combined vaccine+axitinib therapy yields superior antitumor efficacy in a murine melanoma model. Melanoma research. 2012;22(3):236-43.
- Zhao X, Bose A, Komita H, Taylor JL, Chi N, Lowe DB, Okada H, Cao Y, Mukhopadhyay D, Cohen PA, Storkus WJ. Vaccines targeting tumor blood vessel antigens promote CD8(+) T cell-dependent tumor eradication or dormancy in HLA-A2 transgenic mice. Journal of immunology (Baltimore, Md. : 1950). 2012;188(4):1782-8.
- Zhao X, Bose A, Komita H, Taylor JL, Kawabe M, Chi N, Spokas L, Lowe DB, Goldbach C, Alber S, Watkins SC, Butterfield LH, Kalinski P, Kirkwood JM, Storkus WJ. Intratumoral IL-12 gene therapy results in the crosspriming of Tc1 cells reactive against tumor-associated stromal antigens. Molecular therapy : the journal of the American Society of Gene Therapy. 2011;19(4):805-14.