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One or more keywords matched the following properties of Paulos, Chrystal
overview Our laboratory focuses on developing novel T-cell immunotherapies for patients with advanced cancer. Our strategy is based on the use of mouse models to develop human clinical trials that effectively harness the patient’s own immune system to kill cancer. We study new ways to improve adoptive cell transfer (ACT) therapy, which involves removal of T cells from the patient, their expansion/manipulation ex-vivo, followed by their return to patient preconditioned with lymphodepletion via chemotherapy agents and/or total body irradiation. Lymphodepletion significantly enhances the efficacy of ACT therapies. However, host conditioning with lymphodepletion is not the only factor that positively impacts clinical outcome. We and other investigators have found that the functional properties of T cells are critical for successful tumor immunotherapy. We have very recently found that CD4 and CD8 T cells that produce IL-17 (Th17 and Tc17 cells, respectively) mediate robust tumor regression. Additional investigation revealed that the expansion of Th17/Tc17 cells with the costimulatory molecule ICOS but not CD28 further improved their function and their ability to eradiate large tumors (see Fig1). Although ICOS-expanded Th17/Tc17 cells mediate potent tumor regression, the cellular, biochemical and molecular mechanisms underlying how ICOS signaling drives the differentiation and expansion of cells that produce high levels of IL-17, IL-21 and IFN-gamma compared to those stimulated with CD28 remains incompletely elucidated. Thus, we are now investigating key transcription factors regulated by ICOS versus CD28 that distinctly impact their functional fate. We are also investigating the mechanism governing the in vivo effectiveness of ICOS-expanded tumor-specific Tc17/Th17 cells using the clinically relevant transgenic ACT mouse models of cancer created in Dr. Nicholas Restifo’s laboratory. In summary, research in the Paulos laboratory will focus on broadening the utility and efficacy of the ACT approach. We are particularly interested in improving host preconditioning regimens as well as augmenting various T-cell subsets by ex-vivo and in-vivo manipulation with novel cytokine/chemical cocktails and with ICOS agonists (as well as with other costimulatory molecules). We believe that our investigations will provide vital information on how to build on the next generation of T-cell based immunotherapies for cancer as well as for autoimmunity and infectious diseases.
One or more keywords matched the following items that are connected to Paulos, Chrystal
Item TypeName
Academic Article Interleukin-2-dependent mechanisms of tolerance and immunity in vivo.
Academic Article IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy.
Academic Article A human memory T cell subset with stem cell-like properties.
Academic Article Ex vivo interleukin-12-priming during CD8(+) T cell activation dramatically improves adoptive T cell transfer antitumor efficacy in a lymphodepleted host.
Academic Article Type 17 CD8+ T cells display enhanced antitumor immunity.
Concept Interleukin-2 Receptor alpha Subunit
Concept Interleukin-15
Concept Receptors, Interleukin-2
Concept Interleukin-5
Concept Interleukin-7
Concept Interleukin-2
Concept Receptors, Interleukin-7
Concept Interleukin-17
Concept Interleukin-1beta
Concept Interleukin Receptor Common gamma Subunit
Concept Interleukin-6
Concept Interleukin-12
Academic Article Reducing CD73 expression by IL1?-Programmed Th17 cells improves immunotherapeutic control of tumors.
Academic Article Interleukin-12 enhances the function and anti-tumor activity in murine and human CD8(+) T cells.
Academic Article The inducible costimulator augments Tc17 cell responses to self and tumor tissue.
Academic Article Dendritic Cells in Irradiated Mice Trigger the Functional Plasticity and Antitumor Activity of Adoptively Transferred Tc17 Cells via IL12 Signaling.
Academic Article Harnessing the IL-7/IL-7Ra axis to improve tumor immunotherapy.
Academic Article Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic.
Academic Article IL-2Ra mediates temporal regulation of IL-2 signaling and enhances immunotherapy.
Academic Article Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells.
Academic Article Murine Th17 cells utilize IL-2 receptor gamma chain cytokines but are resistant to cytokine withdrawal-induced apoptosis.
Academic Article IL-2 and Beyond in Cancer Immunotherapy.
Academic Article Enhanced Lymphodepletion Is Insufficient to Replace Exogenous IL2 or IL15 Therapy in Augmenting the Efficacy of Adoptively Transferred Effector CD8+ T Cells.
Academic Article In Vitro Priming of Adoptively Transferred T Cells with a ROR? Agonist Confers Durable Memory and Stemness In Vivo.
Academic Article Molecular properties of gp100-reactive T-cell receptors drive the cytokine profile and antitumor efficacy of transgenic host T cells.
Academic Article IL6 Fuels Durable Memory for Th17 Cell-Mediated Responses to Tumors.
Academic Article Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.
Academic Article Dual IL-6 and CTLA-4 blockade regresses pancreatic tumors in a T cell and CXCR3-dependent manner.
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